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Significant progress in the field of VaD resulted from publication of the NINIDS-AIREN Diagnostic Criteria for VaD (G.C. Roman, T.K. Tatemichi, T. Erkinjuntti, et al., Vascular dementia (VaD): diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology 43 (1993) 250-260). Epidemiological studies confirmed the importance of VaD as the second most common cause of dementia in the elderly, representing 15-20% of all cases of dementia. In Europe and North America, Alzheimer's disease (AD) predominates over VaD in a 2:1 ratio; in contrast, in Japan and China VaD accounts for almost 50% of all dementias. Case-control studies have identified risk factors for VaD including ageing, hypertension, diabetes mellitus, hyperlipidemia, recurrent stroke, cardiac disease, smoking, sleep apnea, and more recently, hyperhomocysteinemia, among others. Hypertension treatment may prevent VaD and AD. This finding has enormous importance from the Public Health viewpoint to decrease the future number of patients with dementia in the elderly. Along with advances in the field of VaD came a number of controversies and damaging misconceptions and myths. Myth no. 1--Vascular dementia is a non-entity: The false idea that VaD does not exist is particularly destructive because it creates the perspective that VaD is unworthy of study or research. A condition that either does not exist or represents only a minute proportion of all cases of dementia in the elderly, lacks public health relevance and becomes a low priority for research by funding agencies and industry. In fact, vascular brain lesions are the commonest and most important component of dementia in the elderly. Myth no. 2--Vascular dementia is so difficult to diagnose that only experts can recognize and identify it accurately: VaD does exist and the diagnosis of post-stroke VaD, in particular is straightforward. Most cases fulfill NINDS-AIREN criteria for probable VaD; i.e., (1) there is acute onset of dementia demonstrated by impairment of memory and two other cognitive domains, such as orientation, praxis or executive dysfunction; (2) relevant cerebrovascular lesions are demonstrated by neuroimaging; and (3) a temporal relation between stroke and cognitive loss is evident. In the donepezil trials on VaD, post-stroke dementia represented about 75% of the >1,200 patients enrolled. Myth no. 3--Improvement in clinical trials of cholinergics in VaD is due to underlying AD, not to the vascular lesions. Experimental, clinical and pathological evidence has demonstrated cholinesterase deficits in VaD (independently of any concomitant AD pathology), including low acetylcholine in cerebrospinal fluid, and reduced choline acetyltransferase (ChAT) in the brain.
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PMID:Facts, myths, and controversies in vascular dementia. 1553 19

Preliminary results demonstrate the feasibility and safety of laparoscopic biliopancreatic diversion with duodenal switch, knowing that the superobese patient carries a higher risk than the normal population or the regular obese patient. Future studies with larger numbers of patients should be able to demonstrate the effectiveness this procedure in reducing weight and comorbidities such as hyperlipidemia, hypertension, sleep apnea, and diabetes mellitus, an effectiveness of that has been proven in an open approach. There is currently poor evidence regarding this effective due to small case series and early follow-up. Further research is needed to examine long-term efficacy, with a high priority given to randomized controlled trials.
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PMID:Laparoscopic biliopancreatic diversion with duodenal switch. 1561 35

Obesity, now an epidemic in the USA, northern Europe, and Italy, is associated with several co-morbidities that shorten life expectancy, in particular type 2 diabetes mellitus (T2DM), arterial hypertension, and hyperlipidemia. The impact of obesity on mortality is evident in all ages, and is especially strong in young persons. Obesity, especially visceral obesity, associated with a sedentary lifestyle, is among the strongest risk factors for T2DM, and a diagnosis of T2DM seems to increase linearly as a function of duration of obesity. The pathogenesis of T2DM is based on a dual defect, i.e. increased insulin resistance coupled with defective insulin release. The main abnormality in obesity is increased insulin resistance, while insulin release, even though defective compared with body needs, is usually abundant. The incidence of obesity among children aged 6-16 years is now even greater than that among adults: in Italy, figures up to 30% have been reported. As in adults, obesity is a cause, among children, of arterial hypertension, left ventricular hypertrophy, hyperlipidemia, non-alcoholic-steato hepatitis, sleep apnea syndrome (SAS), and orthopedic, psychological, and social problems. Together with an increase in body weight, there is an increase of visceral fat. Obesity in children has also led to a tremendous increase in the prevalence of impaired glucose tolerance (IGT); the percentages span from 25% in a multiethnic cohort in the USA, to 4% in Italian Caucasians. Management of obesity and of T2DM in children has to face the issue of poor compliance; there is consensus that dietary treatment of obese T2DM children is a failure, so that drugs are required; the only drug evaluated in a formal trial is metformin, that behaves in terms of efficacy and of minor side effects as in adults. In conclusion, obesity in children is not pure obesity, but is accompanied by co-morbidities that cluster to form the "metabolic syndrome" just like in the adults. If this epidemics continues and is not properly challenged, in the next decades we will face an epidemic of early cardiovascular morbidity and mortality.
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PMID:Type 2 diabetes mellitus is becoming the most common type of diabetes in school children. 1566 74

The challenges of the epidemic are not limited to concerns about bulk and weight. The disabilities caused by obesity are physiologic and psychosocial. The increased waist to hip girth is associated with increased risk of cardiovascular disease, hyperlipidemia, hypertension, and diabetes. Obesity also has been related directly to increased risk of sleep apnea, cancer, gallbladder disease, musculoskeletal disorders, severe pancreatitis, bacterial panniculitis, diverticulitis, infertility, urinary incontinence, and idiopathic intracranial hypertension. The psychosocial factors and quality of life in the obese population also have been documented. Although there is some debate, the obese have been found to be twice as likely to suffer from anxiety, impaired social interaction,and depression when compared with the nonobese population. Although advances in obesity surgery have resulted in long-term, lasting treatment of this disease and some of its comorbidities (ie, diabetes, hypertension, sleep apnea), There is a pressing need to develop a comprehensive medical and nutrition plan to reduce the prevalence of this newly identified disease state. Some draw parallels to tobacco and the morbidity and mortality associated with its use. Perhaps there are similarities in these two epidemics. Both start with education of the population as to the morbidities and mortality associated with the disease. As with tobacco, this education is especially important for youth. Without a plan of education to promote nutrition and increased physical activity, and continued research into the causes of obesity, the prevalence of obesity will continue to rise in the United States.
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PMID:Epidemiology of obesity in the United States. 1582 34

Non-alcoholic steatohepatitis (NASH) is one of the most common liver disorders. This is highly prevalent in obese and diabetic subjects. Persons with central obesity are at particular risk. Other clinical predictors are age more than 40-50 years and hyperlipidemias, but none of these factors is invariable for causation of NASH. Other reported associations are, celiac disease, Wilson's Disease and few other metabolic diseases. Drugs, particularly amiodarone, tamoxifen, nucleoside analogues and methotrxate have also been linked to NASH. The disease is evenly distributed in both sexes but advanced disease is more common in women. Ethnic variation exists and African Americans are less affected than Hispanic Americans. Specific clinical features of NASH are infrequent. Patients usually come to clinical attention by elevated liver enzymes found on routine evaluation but on history, about two third of patients will admit to have mild fatigue and about half will report right upper quadrant pain. Rarely, patient may present with a complication of cirrhosis. Physical examination may reveal hepatomegaly and splenomegaly. Research in last few years has stressed that development of steatosis, stetohepatitis, fibrosis with subsequent cirrhosis are most probably the result of insulin resistance. Therefore, clinical features may reflect existence of insulin resistance. Obesity, particularly central obesity is most important of these. Patients may have sleep apnea syndrome. Hypertension and manifestations of diabetes mellitus like polyuria, polydypsia, and neurological deficits may occur. Patients may have varying combination of obesity, diabetes, hyperlipidemia, hypertension and impaired fibrinolysis (syndrome X). Children with insulin resistance may show acanthosis nigricance. Patients with polycystic ovary syndrome, which consists of insulin resistance, diabetes, obesity, hirsutism, oligo or polymenorrha and hyperlipidemia may have NASH. Other rare manifestations of insulin resistance, which can be seen in patients of NASH are lipomatosis, lipoatrophy/lipodystrophy and panniculitis. Most other rare conditions known to cause NASH like peroxisomal diseases, mitochondialpathies, Weber-Christian disease, Mauriac syndrome, Madelung's lipomatosis and abetaliopprotenemia also have insulin resistance. This is believed that primary defect underlying insulin resistance is impairment in postreceptor pathways (through tyrosine kinase activity) of insulin action. Primary defect in insulin receptors appear uncommon. This results in down regulation of insulin receptor substance 1 (IRS-1) signaling by excess free fatty acids. In muscle, activated IRS-1 promotes translocation of glucose transporter protein 4 (GLUT4) to cell membrane. As a result, monocyte glucose uptake by GLUT4 increases glucose disposal from blood and reduced need for insulin. PKC-0 is a likely candidate as serine kinase in muscle regulated by fatty acids that can impair the activation of IRS-1. Insulin resistance is usually evaluated by fasting insulin levels, Quantitative Insulin Check Index (QUICKI) and Homeostasis Model Assessment of Insulin Resistance (HOMA), C-peptid/insulin ratio oral glucose tolerance test and hyper insulinemic euglycemic clamp. The clamp technique is considered the gold standard.
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PMID:Insulin resistance and clinical aspects of non-alcoholic steatohepatitis (NASH). 1619 20

In the United States, obesity has reached epidemic proportions. Serious medical complications, impaired quality of life, and premature mortality are all associated with obesity. Medical conditions such as type 2 diabetes mellitus, hypertension, hyperlipidemia, or sleep apnea can improve or be cured with weight loss. Medical treatment programs focused on diet, behavior modification, and/or pharmacologic intervention have met with limited long-term success. Although surgical treatments for obesity have become popular in recent years, they should only be used as a last resort for weight loss. Not all patients can be considered appropriate candidates for surgery; therefore, guidelines based on criteria from the National Institutes of Health should be used preoperatively to help identify suitable persons. Most individuals who opt for weight-loss surgery have usually struggled for many years with losing weight and keeping it off, but surgery alone will not ensure successful weight loss. Patient education is imperative for long-term success. Moreover, any such educational regimen should include information on diet, vitamin and mineral supplementation, and lifestyle changes, as well as expected weight-loss results and improvements in comorbid conditions. Patients must be willing to commit to a long-term follow-up program intended to promote successful weight loss and weight maintenance and to prevent metabolic and nutritional complications.
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PMID:Surgical treatment for obesity: ensuring success. 1630 6

Polycystic ovary syndrome (PCOS) is a syndrome, which can be defined as a group of recognisable patterns of symptoms or abnormalities that indicate a particular medical situation. The current definition of PCOS requires the presence of two of the following three conditions: (i) oligo- and/or anovulation; (ii) clinical and/or biochemical signs of hyperandrogenism; and (iii) polycystic ovaries--and the exclusion of other aetiologies. It is generally accepted that the prevalence of PCOS is approximately 5-10%, and that of polycystic ovaries alone is 21-23%. Other features of PCOS are obesity, insulin resistance, impaired glucose tolerance and type 2 diabetes mellitus, dyslipidaemia, cardiovascular disease, obstructive sleep apnoea and infertility. An approach to a patient with possible PCOS should be directed towards making a diagnosis and screening for associated endocrine abnormalities. Therapeutic interventions are directed towards addressing the needs of the patient at present and towards preventing long-term complications of the syndrome. Body mass index, which is a primary mediator in the relationship between PCOS and health-related quality of life in obese PCOS adolescents, may play a similar role in other PCOS patients. Any intervention directed at reducing central obesity will not only improve quality of life but also correct hyperinsulinism and improve fertility and lipid and androgen profiles. It is also the only currently available intervention that can have a lifelong impact on reducing possible long-term complications of the syndrome. Lifestyle modification is the cardinal intervention. Pharmacological treatments are available for specific indications. Infertility can be treated with clomifene (clomiphene citrate), metformin, gonadotropins or surgery to the ovaries. Cyproterone (alone or in combination with ethinylestradiol) and spironolactone are the main drugs used in the treatment of hirsutism. Other drugs that can be considered include flutamide, ketoconazole and finasteride. Women with PCOS require ongoing surveillance to detect impaired glucose tolerance, hyperlipidaemia, endometrial hyperplasia and consequent complications. Obese women, in particular, require regular glucose tolerance testing because of the potential for rapid progression from normal to impaired glucose tolerance and diabetes. The focus of this article is the epidemiology, diagnosis and management of this common endocrine disorder. Diagnostic and co-morbid features are discussed separately to facilitate understanding of PCOS. Symptom-directed strategies, as well as short- and long-term goals of treatment, are outlined.
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PMID:Diagnosis and management of polycystic ovary syndrome: a practical guide. 1674 5

Surgical results, economic consequences, and shortterm health of obese patients were evaluated before and after bariatric surgery. Of 35 patients in Mayo Health Plan Arizona eligible for bariatric surgery and scheduled for gastric restriction with Roux-en-Y gastrojejunostomy, 22 (7 men, 15 women) completed pre- and postoperative (6- and 12-mo) short form (SF)-12 Health Surveys. Nineteen patients had open bariatric procedures and 3 had laparoscopic procedures. Comorbid conditions, hospital course, weight loss, and complications were examined. Health care utilization (actual dollars paid by plan) for the preceding year and at 1- and 2-yr follow-up were compared. Major comorbid conditions included diabetes mellitus or impaired fasting glucose, hyperlipidemia, sleep apnea, and hypertension. Mean length of hospital stay was 4.8 d after open procedures and 2 d after laparoscopic procedures. No serious operative or postoperative complications occurred. From a baseline average body mass index (BMI) of 51.9, the 6- and 12-mo BMI averages were 39.6 (23.7% decrease) and 35.3 (32% decrease), respectively. Both physical and mental status improved. From baseline, physical health changed 18 and 21.2 points at 6 and 12 mo, respectively (p < 0.001), and mental health changed 9.3 points at each interval (p =0.003). Each postoperative year, resource utilization decreased (mean= $1300 per patient). Our findings of good surgical outcomes, significant weight loss, improved health status, and potential financial savings in this small sample may help patients, insurers, and self-funded employer groups evaluate the appropriateness of bariatric procedures.
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PMID:Outcomes, health status, and medical resource utilization after bariatric surgery. 1678 80

A number of factors are known to be associated to an increased risk of cardiovascular disease. High blood pressure, lipid abnormalities, type 2 diabetes mellitus, obesity and sleep apnea may act as isolated risk factors but, frequently, coexist in the same person. Studies involving surgery aimed at weight reduction (bariatric surgery - from barys, the greek term for heavy) have consistently shown a high probability of resolution of major risk factors, namely of diabetes, hyperlipidemia and hypertension, associated to weight reduction. Data in a similar direction were obtained after weight reduction was reached by means of pharmacological therapy. Excessive weight thus may stand as the probable cause for a number of cardiovascular risk factors, at least in many patients with an adequate genetic background. The moment may have come to focus on causality and to suggest that the risk factor association syndrome, in patients with overweight/obesity, may be defined as the systemic consequences of excessive weight, including hormonal, body habitus, metabolic, hemodynamic and respiratory parameters. A suitable name for the syndrome might be the barisystemic syndrome.
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PMID:The risk factor association syndrome as a barisystemic syndrome: a view on obesity and the metabolic syndrome. 1702 3

Obesity and overweight, as a part of the metabolic syndrome, are well known risk factors for the development of diabetes, hypertension, coronary heart disease, hyperlipidemia, stroke, sleep apnea syndrome, osteoarthritis and certain forms of cancer. Cardiovascular disease remains the leading killer in industrialized countries, where it accounts for 40% of deaths. Obesity is defined either by increased waist circumference, waist to hip ratio, or body mass index. Obesity results from an interaction of genes and lifestyle. As people in both developed and developing countries eat more and more energy dense food, and have ever less physical activity, the number of overweight and obese people increases to epidemic proportions. Abdominal obesity plays a key role in the pathophysiology of metabolic disorders, is associated with insulin resistance, and predicts the development of type 2 diabetes and subsequent coronary artery disease. In the general population, obesity is associated with an increased mortality, but paradoxically, a positive correlation between body mass index and survival in congestive heart failure has been reported. In secondary prevention, obesity is underrecognized, underdiagnosed and undertreated in persons with cardiovascular diseases. Weight loss and prevention of weight gain have to be considered one of the most important strategies to reduce the incidence of cardiovascular disease. Increased physical activity and appropriate diet are the cornestones of treatment. Considering the high prevalence of overweight and obesity in Croatia, there is urgent necessity to improve the level of knowledge and skills in understanding obesity by health care services, and to implement appropriate professional strategy to achieve the desired lifestyle modifications.
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PMID:[Obesity--a global public health problem]. 1758 71


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