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Query: UMLS:C0028754 (obesity)
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Liver transplant recipients have an increased risk for cardiovascular disease because of a high incidence of obesity, arterial hypertension, diabetes mellitus, and hyperlipidemia. Hyperhomocysteinemia has been found to be an important risk factor for cardiovascular disease in large studies. Fasting serum levels of homocysteine were measured in 105 liver transplant recipients, and hyperhomocysteinemia was defined as a fasting serum homocysteine level greater than 13 micromol/L. Patients with versus without hyperhomocysteinemia were compared. The possible association of hyperhomocysteinemia with age, sex, cause of liver disease, time elapsed since liver transplantation, immunosuppressive therapy, folic acid level, liver function test results, renal function, and other cardiovascular risk factors was investigated. Patients with serum homocysteine levels greater than 15 micromol/L were treated with folic acid, 10 mg/d, and serum homocysteine levels were measured again 1 to 3 months later in 10 patients. Hyperhomocysteinemia was detected in 28 patients (27%). In univariate analysis, it was associated with hepatitis C virus infection, treatment with mycophenolate mofetil, and greater serum levels of alkaline phosphatase, gamma-glutamyl transpeptidase, urea, and creatinine. In multivariate analysis, only greater serum levels of creatinine (P =.006) were associated with hyperhomocysteinemia. Treatment with folic acid resulted in a decrease in fasting serum homocysteine levels in 9 of the 10 patients tested (P =.01). Hyperhomocystinemia, associated with renal dysfunction, is a frequent finding in liver transplant recipients. Treatment with folic acid may reduce fasting homocysteine levels.
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PMID:Hyperhomocysteinemia in liver transplant recipients: prevalence and multivariate analysis of predisposing factors. 1098 61

A variety of evidence implicates the orexins, especially orexin-A, in the regulation of food intake, but it has not been established whether this effect is mediated by the orexin-1 or orexin-2 receptor. In the present study, a selective orexin-1 receptor antagonist, 1-(2-methylbenzoxazol-6-yl)-3-[1,5]naphthyridin-4-yl urea hydrochloride (SB-334867-A), was administered intraperitoneally to rats under various conditions, and food consumption was subsequently measured over 24 h. In male rats, a single dose of SB-334867-A (30 mg/kg, i.p.) given during the light phase reduced both orexin-A-induced food intake (7 nmol, i.c.v.) and feeding stimulated by an overnight fast for 4 h. When given at the start of the dark phase, food consumption was reduced in both male and female rats over 24 h. Daily injections at the start of the dark phase for 3 days reduced natural feeding in male rats over 24 h on days one and three. These findings demonstrate direct inhibition of orexin-A induced food intake with a selective orexin-1 receptor antagonist. Furthermore, the suppression of nocturnal feeding and food intake stimulated by an overnight fast supports other evidence that orexin-A is involved in the regulation of natural feeding and suggests that orexin-1 receptor antagonists could be useful in the treatment of obesity.
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PMID:A selective orexin-1 receptor antagonist reduces food consumption in male and female rats. 1110 51

White blood cell (WBC) count has been shown as a risk factor for cardiovascular disease. Decreased insulin sensitivity has been suggested as the link between these two entities. Our aim was to study the potential relation between insulin sensitivity and WBC count in patients with coronary artery disease. In order to assess insulin sensitivity, we performed 83 insulin suppression tests before and after therapy in 50 patients with coronary artery disease. Patients with glucose intolerance, arterial hypertension or obesity were excluded. Steady-state plasma glucose (SSPG) and insulin sensitivity index (ISI=1 000 x glucose infusion rate/SSPG) were considered as a measure of insulin sensitivity. WBC count, blood platelets, fibrinogen, microalbuminuria, creatinine, urea and HbA1c were also assessed. Simple and multiple correlation analysis were carried out between insulin sensitivity parameters and the other variables measured. There were significant correlation between SSPG and WBC count (r=0,32: p=0,003) and microalbuminuria (r=0,28: p=0,012). We also found statistically significant correlation between ISI and WBC count (r=0,27: p=0,015) and microalbuminuria (r=0,24: p=0,029). No correlation could be detected between either SSPG or ISI and the other variables measured. In multiple regression analysis, WBC count was found to be an independent predictor of both SSPG (p<0.01) and ISI (p<0.05). Our data show the existence of a significant relationship between decreased insulin sensitivity and WBC count in patients with coronary artery disease. The results of this study suggest that an elevated WBC count could be postulated as part of the insulin resistant syndrome.
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PMID:White blood cell count and insulin resistance in patients with coronary artery disease. 1124 Apr 2

To identify the factors responsible for increases in serum uric acid (SUA), a cohort of 1,312 hyperuricemia-free (SUA < 7.5 mg/dL and no medication for hyperuricemia or hypertension) male office workers aged 30 to 52 years were examined annually for 8 successive years. Subjects who were found to have become hyperuricemic (SUA > or = 7.5 mg/dL) or who started medication for hyperuricemia during repeat surveys were defined as incidence cases. The SUA trend was also examined in 1,062 subjects for whom 9 consecutive SUA values were available and who did not start medication for hyperuricemia or hypertension during the observation period. Multivariate analyses, excluding the baseline SUA level as a factor in the Cox proportional-hazards model, indicated that age (negative), body mass index (BMI), log triglyceride level, hemoglobin A(1c) (HbA(1c)) level (negative), white blood cell count, and alcohol intake at study entry were significantly associated with the incidence of hyperuricemia. In the model including the baseline SUA level, baseline SUA level was the strongest factor for the incidence of hyperuricemia, and BMI, white blood cell count, and alcohol intake at study entry remained as independent factors. From stepwise linear regression analyses for SUA slope, excluding the baseline SUA level as a factor, significant correlates with SUA slope were, in order of their relative importance, slopes of BMI, HbA(1c) (negative), blood urea nitrogen, log triglyceride level, total protein, and baseline levels of hematocrit (negative), white blood cells, and HbA(1c) (negative). In stepwise linear regression analyses, including the baseline SUA level as a factor, SUA level (negative) and alcohol intake at study entry emerged as significant factors for SUA slope. The cumulative percentage of variation for SUA slope was 25.6%. In conclusion, obesity, alcohol intake, and multimetabolic disorders were determined to be independent predictors for the development of hyperuricemia. In addition, the white blood cell level may be a contributory factor.
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PMID:Predictors for development of hyperuricemia: an 8-year longitudinal study in middle-aged Japanese men. 1139 34

An 11-year-old boy suffering from morbid obesity since infancy developed at age 9 a progressive brown-black hyperpigmentated and hyperkeratotic eruption in the neck and axillary region with minor involvement of both groins. Based on this clinical picture, and confirmed by histopathology, we diagnosed acanthosis nigricans. Following a thorough endocrinological examination and because the patient's obese mother showed similar skin lesions, the disease was subclassified as a familial obesity-associated type of acanthosis nigricans associated with insulin resistance. In a right-left-comparison the affected skin of one body side was treated with tazarotene 0.05% versus urea 10%, once daily each. A great benefit for the tazarotene-treated over the opposite side could already be seen after three weeks which was also verified by dermatohistopathology. Three months after topical tazarotene treatment had been extended to both sides, the residual lesions were significantly improved. The highly satisfying, good result has been maintained up to now by a continuous topical retinoid treatment over 18 months, usually with an interval application regimen, i.e., 3 x per week.
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PMID:[Successful symptomatic tazarotene treatment of juvenile acanthosis nigricans of the familial obesity-associated type in insulin resistance]. 1142 78

Vegetarians have lower blood pressure and lower cardiovascular mortality. Vegetarian diets may have lower cardiovascular risks through positive influence on endothelium-dependent relaxation and related functions. The objectives of this study were to assess the differences of vascular dilatory functions between middle-aged vegetarians and sex and age-matched omnivores before they develop any clinical manifestations of atherosclerosis. Twenty healthy vegetarians over the age of 50 and 20 healthy omnivores over the age of 50 were recruited for this study. Subjects with known risk factors for atherosclerosis such as hypertension, diabetes, obesity, hypercholesteremia, cigarette smoking, family history of vascular diseases, or taking any regular medication were excluded. Medical history, body weight, height, and duration of vegetarian diet were recorded. Baseline CBC, urinalysis and biochemical data such as fasting blood glucose, thyroid function, blood urea nitrogen, creatinine, serum electrolytes (sodium, potassium, chloride, calcium and magnesium), lipid profiles [total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol] were obtained after a 14 h fast. Blood pressures and heart rate were recorded in supine position. Vascular dilatory functions, both flow-mediated (endothelium-dependent) and nitroglycerin-induced (endothelium-independent), were evaluated by using a non-invasive ultrasonographic method. The results show that there were no significant differences in the baseline characteristic between the vegetarians and the omnivores. There were also no significant differences in serum glucose, lipid profiles and thyroid function between these two groups. However, vasodilatation responses (both flow-mediated and nitroglycerin-induced) were significantly better in the vegetarian group and the degree of vasodilatation appeared to be correlated with years on vegetarian diets. Our findings suggest that vegetarian diets, by themselves, have a direct beneficial effect on vascular endothelial and smooth muscle function and may help to account for the lower incidence of atherosclerosis and cardiovascular mortality.
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PMID:Vascular dilatory functions of ovo-lactovegetarians compared with omnivores. 1150 Jan 98

A single dose of the orexin-1 (OX1) receptor antagonist 1-(2-methylbenzoxazol-6-yl)-3-[1,5] naphthyridin-4-yl urea hydrochloride (SB-334867-A) reduces orexin-A-induced feeding and natural feeding in Sprague Dawley rats. In this study, the anti-obesity effects of SB-334867-A were determined in genetically obese (ob/ob) mice dosed with SB-334867-A (30 mg/kg, i.p.) once daily for 7 days, and then twice daily for a further 7 days. SB-334867-A reduced cumulative food intake and body weight gain over 14 days. Total fat mass gain, determined by Dual Emission X-ray Absorptiometry, was reduced, while gain in fat-free mass was unchanged. Fasting (5 h) blood glucose was also reduced at the end of the study, with a trend to reduced plasma insulin. Interscapular brown adipose tissue (BAT) weight was reduced, the tissue was noticeably darker in colour and quantitative PCR (TaqMan) analysis of this tissue showed a trend to an increase in uncoupling protein-1 mRNA expression, suggesting that SB-334867-A might stimulate thermogenesis. This was confirmed in a separate study in which a single dose of SB-334867-A (30 mg/kg, i.p.) increased metabolic rate over 4 h in ob/ob mice. OX1 receptor mRNA was detected in BAT, and its expression was increased by 58% by treatment with SB-334867-A. This is the first demonstration that OX1 receptor antagonists have potential as both anti-obesity and anti-diabetic agents.
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PMID:Anorectic, thermogenic and anti-obesity activity of a selective orexin-1 receptor antagonist in ob/ob mice. 1183 Feb 90

Large prospective epidemiologic studies have shown that long-term use of oral contraceptives containing estrogen induce an increase in blood pressure and sharply increase the risk of hypertension. Susceptibility to the hypertensive effects of oral contraceptives is heightened where risk factors such as age, family history of hypertension, preexisting or occult renal disease, parity and obesity exist. Hypertension among pill users usually develops within the first 6 months of usage and occasionally is delayed for as long as 6 years. Anitihypertensive therapy is seldom needed as the hypertension that developes is generally mild and uncomplicated, and rapidly reverses when the pills are discontinued. However, a small percentage of patients develop severe, even life-threatening hypertension and the hypertensive effects are felt long after the pills are discontinued. Cases of malignant hypertension and irreversible renal failure requiring maintenance hemodialysis, bilateral nephrectomy, and renal transplantation have occurred following administration of oral contraceptive pills. The mechanism by which oral pills induce hypertension in susceptible women is not known and needs further research. Before oral contraceptives are prescribed, physicians should take a careful history and perform a detailed physicial examination with special attention to the cardiovascular system. Multiple blood pressure measurements should be made and routine laboratory studies including urinalysis, blood urea and nitrogen and serum creatinine should be performed. It is preferable to start with a relatively low (50 mcg) estrogenic content preparation. Patients who develop hypertension (diastolic pressure, 90 mm Hg) on oral contraceptives should stop taking the pills immediately, and should be considered to have estrogen-induced hypertension. They should never again receive estrogen-containing oral pills, although they can try pills containing only progestogen. There is no contraindication to pregnancy in these patients, as most women who become hypertensive on oral pills go on to have normotensive pregnancies. Pregnancy in women who are susceptible to essential hypertension however should be treated as high risk.
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PMID:Hypertension and oral contraceptives. 1226 83

To investigate the relationship between obesity, small-solute clearances, and nutrition in continuous peritoneal dialysis (CPD), we compared clearances and nutrition indices between 270 obese and 502 normal-weight CPD patients. Degree of obesity was classified by the ratio of body weight (W) to desired weight (DW) at the first clearance study. The DWs were obtained from the tables of the Metropolitan Life Insurance Company, assuming a medium skeletal frame. The obese patients (group I) had W/DW > 1.2 (1.38 +/- 0.17), and the normal-weight patients (group II) had 0.9 < or = W/DW < or = 1.2 (1.05 +/- 0.08). Nutrition indices derived from urea nitrogen and creatinine excretion were normalized by both W and DW. The following variables differed between group I (first value) and group II: sex (women: 48.2% vs. 33.9%), W (87.6 +/- 14.4 kg vs. 68.2 +/- 8.7 kg), body surface area (1.95 +/- 0.22 m2 vs. 1.77 +/- 0.16 m2), body water by method of Watson (41.2 +/- 7.7 L vs. 36.3 +/- 5.5 L), body mass index (31.8 +/- 3.9 vs 24.3 +/- 2.0), protein nitrogen appearance (PNA: 62.9 +/- 17.6 kg in 24 h vs. 57.7 +/- 15.7 kg in 24 h), PNA normalized to DW (1.08 +/- 0.29 g/kg in 24 h vs. 0.96 +/- 0.26 g/kg in 24 h), creatinine excretion (CrEx: 1111 +/- 396 mg in 24 h vs. 991 +/- 348 mg in 24 h), CrEx/W (12.6 +/- 3.7 g/kg in 24 h vs. 15.4 +/- 4.5 g/kg in 24 h), CrEx/DW (17.3 +/- 5.3 g/kg in 24 h vs. 15.1 +/- 4.8 g/kg in 24 h), lean body mass (LBM: 49.3 +/- 13.8 kg vs. 43.6 +/- 11.9 kg), LBM/W (0.56 +/- 0.12 vs. 0.64 +/- 0.15), and LBM/DW (0.77 +/- 0.18 vs 0.67 +/- 0.16), all at p < or = 0.034. Marginal differences (0.10 > p > 0.05) were found in the diabetes prevalence (53.0% vs. 40.8%), height (165.9 +/- 11.7 cm vs. 167.4 +/- 9.8 cm), and serum albumin (3.64 +/- 0.55 g/dL vs. 3.53 +/- 0.62 g/dL). No differences were found in age, duration of CPD until the first clearance study, percent of subjects with anuria, Kt/V urea, creatinine clearance, blood urea nitrogen, serum creatinine, and PNA normalized to W. Obese CPD patients tend to have better nutrition indices than do normal-weight CPD patients with similar small-solute clearances. In obese subjects, normalization by W creates inappropriately low values for nutrition indices derived from urea nitrogen and creatinine excretion. Normalization of those indices by DW appears preferable.
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PMID:Small solute clearances and nutrition indices in obese patients on continuous peritoneal dialysis. 1240 84

The pathogenesis of nephrolithiasis in Cushing's syndrome is still not completely clarified. The current study aimed at investigating prevalence of nephrolithiasis and role of different lithogenic factors in Cushing's disease (CD). Forty-six CD patients (24 with active and 22 with cured disease) and 46 sex- and age-matched controls entered the study. Body mass index, blood pressure, fasting glucose and insulin, serum and urinary creatinine, urea, uric acid, electrolytes, and cystine, urinary volume, pH, oxalate, and citrate levels, and renal ultrasonography (US) were performed in all patients and controls. Nephrolithiasis was found in 50% of active patients, 27.3% of cured patients, and 6.5% of controls (P < 0.001). Compared with controls, patients with active disease had a significantly increased prevalence of obesity, arterial hypertension, diabetes mellitus, hypercalciuria, hypocitraturia, and hyperuricosuria, significantly higher levels of serum and urinary cystine, urinary creatinine, urea, uric acid, potassium, calcium, phosphorus, and oxalate, significantly lower levels of urinary citrate levels. Compared with controls, patients cured from CD had a significantly increased prevalence of obesity, systemic arterial hypertension, and diabetes mellitus, whereas urinary citrate was significantly decreased. At multivariate analysis, a significantly increased risk to develop kidney stones was independently associated with urinary excretion of uric acid (odds ratio = 1.6, confidence interval = 1.0-2.5) and systemic arterial blood pressure (odds ratio = 2.6, confidence interval = 1.1-6.6). In conclusion, patients with active CD have an increased prevalence of nephrolithiasis compared with general population, which decreases but not disappears in patients successfully cured from the disease. This complication is likely caused by the synergic effect of different hypercortisolism-dependent metabolic and hemodynamic abnormalities, among which systemic arterial hypertension and excessive urinary uric acid excretion seem to play a pivotal role.
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PMID:Nephrolithiasis in Cushing's disease: prevalence, etiopathogenesis, and modification after disease cure. 1272 57


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