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

Total intravenous anaesthesia (TIVA) with short-acting drugs is a standard procedure for day case surgery and is increasingly used for neurosurgical, cardiac surgical and paediatric surgical operations. The combination of propofol with alfentanil or remifentanil is frequently applied due to its favourable pharmacological properties. Propofol is characterized by a large volume of distribution at steady state and a relatively long elimination half time (t1/2 beta). Because of a high metabolic clearance, the clinical effects of propofol decline rapidly even after prolonged intravenous drug infusion. In patients with increased age, obesity or liver or renal failure, decreased doses of propofol for induction of anaesthesia are recommended. The short-acting opioids alfentanil and remifentanil provide small volumes of distribution at steady state, a short blood-brain equilibration time and decreased t1/2 beta. Remifentanil has unique pharmacological properties due to an ester binding and its elimination via extrahepatic hydrolysis by non-specific blood and tissue esterases. The context sensitive half time of remifentanil is significantly shorter than that of other opioids. Its analgetic potency is equal to fentanyl and 20 to 30 times higher than alfentanil. The advantages of total intravenous anaesthesia include fewer haemodynamic side-effects, a decreased incidence of postoperative nausea and vomiting and less neurohumoral stress response to surgery. Adequate pain therapy is mandatory after total intravenous anaesthesia with short-acting drugs. Continuous infusion of remifentanil for postoperative analgesia or supplementation of regional anaesthesia requires careful monitoring of vital functions. The economic aspects of TIVA remain to be determined.
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PMID:[Perioperative management with short-acting intravenous anesthetics]. 1119 82

Diabetes mellitus is a chronic disease that leads to complications including heart disease, stroke, kidney failure, blindness and nerve damage. Type 2 diabetes, characterized by target-tissue resistance to insulin, is epidemic in industrialized societies and is strongly associated with obesity; however, the mechanism by which increased adiposity causes insulin resistance is unclear. Here we show that adipocytes secrete a unique signalling molecule, which we have named resistin (for resistance to insulin). Circulating resistin levels are decreased by the anti-diabetic drug rosiglitazone, and increased in diet-induced and genetic forms of obesity. Administration of anti-resistin antibody improves blood sugar and insulin action in mice with diet-induced obesity. Moreover, treatment of normal mice with recombinant resistin impairs glucose tolerance and insulin action. Insulin-stimulated glucose uptake by adipocytes is enhanced by neutralization of resistin and is reduced by resistin treatment. Resistin is thus a hormone that potentially links obesity to diabetes.
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PMID:The hormone resistin links obesity to diabetes. 1120 21

The present state of knowledge about growth hormone binding proteins (GHBP) is reviewed, with particular emphasis on the high affinity GHBP, which represents the circulating ectodomain of the growth hormone receptor (GHR). GHBP is conserved through vertebrate evolution, is produced in many tissues (especially liver) by either alternative GHR mRNA splicing (rodents) or by proteolytic cleavage from the GHR (humans, rabbits and several other species). The metalloprotease TACE (tumor necrosis factor-alpha converting enzyme) is the likely enzyme responsible for cleavage, but the structural requirements for TACE recognition or catalysis, and hence the precise cleavage point in the GHR, are unknown. GHBP is widely distributed in biological fluids, with marked concentration differences amongst them. GHBP binds about half of the circulating GH under basal conditions but is easily saturated at high GH levels; it subserves complex functions, including a circulating buffer/reservoir function for GH, prolongation of plasma GH half-life, competition with GHRs for GH, and probably unproductive heterodimer formation with the GHR. The net effect of these partly enhancing and partly inhibitory functions on GH action in vivo is complex and difficult to ascertain. Serum GHBP levels roughly parallel GHR expression (particularly in liver) through the life span, with very low levels in fetal life, upregulation to adult levels during childhood, and decline in senescence. Rodent pregnancy is associated with a massive increase in GHBP expression. Although the regulation of GHBP expression/production is not necessarily tightly linked to GHR expression, in general, low GHBP levels occur in conditions associated with GH resistance (e.g., malnutrition, uncontrolled diabetes, catabolic states, renal failure, hypothyroidism). Conversely, obesity, a condition with enhanced GH responsivity, is associated with elevated GHBP levels. This suggests that in many (but not all) instances of abnormal GH action, the GHBP level reflects GHR status. Laron syndrome (genetic GHR deficiency/dysfunction due to mutations in the GHR gene) is associated with low or undetectable GHBP in 75-80% of patients; GHBP measurement can therefore be used diagnostically. Depending on the design of assays for serum GH, endogenous GHBP may interfere to varying degrees, and GH assays should be individually validated and optimized in this regard. The ultimate biological role and physiological significance of the GHBP remain to be established.
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PMID:Growth hormone binding protein 2001. 1132 70

Hyperhomocysteinemia (HHcy) is a metabolic disorder frequently occurring in the elderly population. Recently several reports have suggested abnormalities in homocysteine (tHcy) metabolism implicating HHcy as a metabolic link in the multifactorial processes characterizing many geriatric illnesses-with special emphasis on atherosclerotic vascular diseases and cognitive impairment. The present study was undertaken in a large sample of elderly hospitalized subjects to determine (1) the prevalence of HHcy, (2) the association of HHcy with vascular and cognitive disorders, and (3) the factors independently predicting Hhcy. Six hundred elderly subjects (264 men and 336 women; mean age, 79 +/- 9 years) were randomly chosen from those admitted as inpatients over a period of 3 years. In all patients, body mass index (BMI), mid-upper arm muscle area (MUAMA), plasma cholesterol, triglycerides, total proteins, albumin, lymphocyte count, creatinine, homocysteine (fasting and 4 hours after methionine oral load), serum vitamin B(6), vitamin B(12), and folate concentrations were measured. The presence of disease or use of medications known to affect homocysteine plasma levels were also recorded. The mean fasting tHcy level was 16.8 +/- 12 micromol/L in the whole sample, 18.18 +/- 13.25 micromol/L in men, and 15.86 +/- 12.14 micromol/L in women (P =.005 men v women). The mean Hcy level 4 hours after methionine load was 37.95 +/- 20.9 in the whole sample. Prevalence of hyperhomocysteinemia (fasting Hcy > or = 15 micromol/L or 4 hours after methionine load > or = 35 micromol/L) was 61% (365/600) (67% in men and 56% in women, P <.05). HHcy was rarely (8%) an isolated disorder; in addition to diabetes (20%), renal failure (48.2%), and malnutrition (20.2%), it was often associated with heart failure (30%), malignancies (20.5%), and the use of diuretics (56%) and anticonvulsant drugs (13%). Plasma homocysteine progressively increases across subjects from those with no diabetes, malnutrition, renal failure, obesity, inflammatory bowel disease, heart failure to those with 1, 2, or more concurrent diseases. Multiple stepwise regression analysis showed that 72% of plasma total fasting tHcy variability was explained by age, serum folate, plasma albumin, use of diuretics, and renal function (measured as plasma creatinine clearance). In conclusion, the present study documents that hyperhomocysteinemia, in elderly hospitalized patients is (1) a common finding, (2) frequently associated with vascular and cognitive disorders, and (3) probably a secondary phenomenon in most cases. The major predictor of high plasma homocysteine levels were age, serum folate, plasma albumin, plasma creatinine clearance, and use of diuretic drugs. These variables explain a large proportion of plasma Hcy variability.
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PMID:Hyperhomocysteinemia and related factors in 600 hospitalized elderly subjects. 1173 95

Patients with end stage renal disease have a high prevalence of cardiovascular disease and coronary arteriography is often routinely performed prior to kidney transplantation. However, the value of the conventional risk factors and non-invasive markers of coronary artery disease (CAD) in triaging patients for coronary arteriography has not been fully examined. 116 patients with end stage renal disease were evaluated. Coronary arteriography was performed in all patients either for a suspicion of CAD or as part of a routine pre-transplant evaluation. Lesions causing > or = 50% luminal diameter stenosis in any of the three major coronary artery systems were considered significant. The mean age was 53.3 +/- 9.3 years. Significant CAD was present in 69 patients (60%). Increasing age, family history of premature ischemic heart disease, the presence of angina, abnormal Q waves on the ECG or abnormal ST segment depression and the presence of coronary calcification were significant markers of coronary artery disease. However male gender, diabetes mellitus and obesity did not correlate with coronary disease. Even though hypertension, hypercholesterolemia and smoking were also not useful predictors these could have been modified by the renal failure. In conclusion increasing age, a family history of premature ischemic heart disease and some non-invasive markers were useful predictors of coronary disease.
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PMID:Predictors of coronary disease in patients with end stage renal disease. 1177 19

Sixteen cases of necrotizing fasciitis were seen at the Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria from 1990 to 2000. Primary craniocervical involvement was recorded in seven patients (five men and two women). The clinical records of five patients were sufficiently detailed to allow us to report their age, aetiology, predisposing illness, clinical features, complications, management regimen and outcome. The patients were aged 30-75 years and in four of them odontogenic infections were the cause of the condition. Hypertension, diabetes mellitus and obesity were the underlying systemic diseases in three cases and the body/angle region of the mandible was the predominant site of the infection on the face. All five cases had involvement of the neck. Mediastinal extension was recorded in three cases. Two patients had complications: one had septicaemia and renal failure and the other developed bone necrosis. Pre-existing ill health, old age, late surgical intervention, and mediastinal and thoracic extension of infection were responsible for the only death. Treatment involved frequent and multiple surgical debridement, aggressive antimicrobial treatment and control of systemic disease. Early recognition, prompt surgical intervention, and aggressive antimicrobial treatment are essential to minimize morbidity and mortality. Rapid progression of infection, financial constraints, delayed referrals from rural clinics and distance to the tertiary hospital caused problems.
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PMID:Craniocervical necrotizing fasciitis in Ile-Ife, Nigeria. 1188 74

In recent years several multicentric prospective studies have demonstrated the efficacy of some therapeutic measures to slow the progression of renal diseases. Inhibition of renin-angiotensin system (RAS) both by ACE inhibitors (ACEI) and angiotensin II receptor antagonists (ARA) is probably the strongest therapeutic alternative: The antiproteinuric effect of these drugs is an excellent surrogate marker and a predictor of the beneficial influences on the progression of renal failure. The type of renal disease, an inadequate control of blood pressure, and the presence of obesity may counteract the beneficial influences of RAS inhibition, whereas early treatment of all patients with significant proteinuria before the appearance of renal insufficiency and combined therapy with an ACEI and an ARA may augment it. Dietary protein restriction is a classic treatment of chronic renal insufficiency whose effectiveness has been validated by multicentric studies. However, a poor compliance of the patient and the risk of malnutrition with very strict protein restriction could limit the benefits of this treatment. Treatment of hyperlipidemia, prevention of obesity, avoidance of smoking, and regular physical exercise are interventions whose therapeutic potential is progressively recognized, particularly in type 2 diabetic nephropathy. Early correction of anemia may contribute to the slowing of renal disease progression. Although further studies are required, the accumulated evidence and the likelihood of additive beneficial effect of these therapeutic measures advise their combined implementation in patients with chronic renal diseases.
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PMID:Slowing the progression of renal failure. 1198 7

Calciphylaxis is a small vessel vasculopathy involving mural calcification with intimal proliferation, fibrosis, and thrombosis. This syndrome occurs predominantly in individuals with renal failure and results in ischemia and necrosis of skin, subcutaneous fat, visceral organs, and skeletal muscle. The syndrome causes significant morbidity in the form of infection, organ failure, and pain. Mortality rates are high. In individuals with renal failure, risk factors for the development of calciphylaxis include female sex, Caucasian race, obesity, and diabetes mellitus. Many cases occur within the first year of dialysis treatment. Several recent reports demonstrate that prolonged hyperphosphatemia and/or elevated calcium x phosphorus products are associated with the syndrome. Protein malnutrition increases the likelihood of calciphylaxis, as does warfarin use and hypercoagulable states, such as protein C and/or protein S deficiency. Recent advances in diagnostic tools and therapeutic strategies have helped in the management of patients with calciphylaxis.
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PMID:Calciphylaxis: emerging concepts in prevention, diagnosis, and treatment. 1210 Apr 55

Assays for natriuretic peptides have received considerable attention as potential screening tests for congestive heart failure and left ventricular dysfunction. However, information regarding the impact of age, sex, and other physiologic characteristics on natriuretic peptide levels is limited. We examined a healthy reference sample of 911 subjects (mean age 55 years, 62% women) from the Framingham Heart Study who were free of hypertension, valvular disease, diabetes, atrial fibrillation, obesity, coronary heart disease, congestive heart failure, and renal failure, and who had normal left ventricular systolic function. Plasma brain natriuretic peptide and N-terminal atrial natriuretic peptide levels were measured, and multivariable regression used to assess correlates of natriuretic peptide levels. The strongest predictors of higher natriuretic peptide levels were older age and female sex. Other multivariable predictors included lower diastolic blood pressure (higher pulse pressure), lower body mass index, and higher left atrial size. Reference limits were then formulated based on the empirical distribution of natriuretic peptide levels by gender both across all ages and partitioned by age. Age-pooled reference limits compared with age-specific limits classified a higher proportion of healthy elderly subjects (17% vs 2.5%), but a lower proportion of healthy young subjects (1% vs 2.5%) as "abnormal." We conclude that interpretation of natriuretic peptide levels should take into consideration gender and possibly age. The reference limits derived from this large, healthy community-based sample will aid in the identification of elevated natriuretic peptide levels in clinical practice.
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PMID:Impact of age and sex on plasma natriuretic peptide levels in healthy adults. 1212 13

Obesity and arterial hypertension are important public health problems. Both overweight and hypertension predispose to cardiovascular diseases, such as myocardial infarction, stroke and renal failure. Moreover, overweight clearly predisposes to hypertension, and thus to an increased prevalence of cardiovascular diseases. This in turn favors inactivity and further weight gain, leading to an exacerbation of cardiovascular disorders. Obesity, hypertension and cardiovascular diseases thus contribute to three corners of a vicious triangle. It is within this conceptual framework that this paper reviews the pathogenesis of obesity-related hypertension, which is highly complex. Many factors act together to promote vasoconstriction and sodium retention. Leptin, free fatty acids and insulin, whose levels are increased in obesity, may act synergistically to stimulate sympathetic activity and vasoconstriction. In addition, obesity-induced insulin resistance and endothelial dysfunction may operate as amplifiers of the vasoconstrictor response. Finally, increased renal tubular reabsorption of sodium may also occur, caused by an increased renal sympathetic nerve activity, the direct effect of insulin, hyperactivity of the renin-angiotensin system and possibly by an alteration of intrarenal physical forces. All together, these factors will lead to sustained hypertension. Because the prevalence of obesity was steadily increasing in the last decades, leading to an increased prevalence of hypertension and cardiovascular disorders, obesity and hypertension will most likely become the health challenges of the twenty-first century.
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PMID:Pathways from obesity to hypertension: from the perspective of a vicious triangle. 1217 26


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