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)

Binding of valproate and palmitate to serum albumin was studied in 29 valproate-treated epileptic patients. The results were compared with similar observations in a reference group of 43 non valproate-treated individuals. The binding affinity for palmitate was decreased (P < 0.0001) resulting in increased availability of long-chain fatty acids (P = 0.008) due to competitive valproate binding in the valproate-treated patients. The findings support a hypothesis on the pathogenesis of obesity as a complication of valproate treatment of epilepsy.
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PMID:Valproate and palmitate binding to serum albumin in valproate-treated patients. Relation to obesity. 824 40

Overweight and obesity are generally considered to have a negative impact on longevity because of their association with many diseases, including hypertension, diabetes, coronary artery disease, osteoarthritis, and certain types of cancer. Nevertheless, some authors, notably Ancel Keys, have concluded that being overweight improves one's chances for longevity. I studied 122 consecutive patients who had comprehensive geriatric assessment with regard to their body mass index, responses to Wolinsky's Nutritional Risk Index, and serum albumin levels. There was a high prevalence of overweight (60% of men and 45.6% of women). This fact, coupled with the observed low prevalence of underweight subjects, tends to support Keys' statement concerning the benefit of being overweight. However, the relative absence of significant obesity supports the impression that significantly obesity reduces prospects for longevity. Although serum albumin measurements were obtained for only 38 subjects, the fact that the value was low in only one instance--in the case of a person who was seriously ill--suggests that obtaining routine serum albumin measurements in ambulatory, community-dwelling elderly people is not cost-effective.
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PMID:Assessment of nutritional status and obesity in elderly patients as seen in general medical practice. 836 44

Protein catabolic rate (PCR) and PCR normalized to standard weight (PCRN) are important indices of nutrition in patients on continuous peritoneal dialysis. The purpose of this study was to test whether urea clearance is among the predictors of PCR and PCRN in a multivariate analysis. Stepwise logistic regression was used to develop separate models for low PCR and low PCRN on a set of 143 urea kinetic studies in 92 patients on continuous peritoneal dialysis. The regression models were tested on an independent sample of 189 urea kinetic studies in 102 patients on continuous peritoneal dialysis by deriving the area under a receiver operating characteristic curve. In the derivation set, low serum urea, high serum creatinine, low urine and dialysate drain volumes, and low body surface area were identified as predictors of PCR < or = 50 g daily. The area under the receiver operating characteristic curve in the validation set was 0.930 (95% confidence interval: 0.915-0.945). Low serum urea, male gender, high body mass index and low urea fractional clearance (KT/V) were predictors of PCRN < or = 0.80 g/kg daily. The receiver operating characteristic area for this model was 0.948 (95% confidence interval: 0.926-0.970). Logistic regression analysis was repeated twice after adding urea nitrogen excretion normalized to standard weight (UNEN) as a candidate variable. This process identified low UNEN, male gender, and obesity as the predictors of low PCRN, and low UNEN, male gender, low urine volume, low drain volume normalized by body water, and high serum albumin as predictors of low KT/V urea. The authors conclude that PCR and PCRN can be predicted by models that incorporate serum azotemic indices, body size and composition, and direct or indirect measurements of urea clearance. Small body size and lean body composition predict low PCR but high PCRN values. Both PCRN and KT/V urea are predicted by UNEN. Multivariate analysis cannot, therefore, rule out the hypothesis that PCRN and KT/V are linked mathematically.
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PMID:Protein catabolic rate in patients on continuous peritoneal dialysis. A multivariate predictive model. 880 58

Inadequate nutrition is a major problem of elderly people today, a rapidly growing segment of western societies. Yet information on the nutritional state of the elderly in the community is much needed. We surveyed the nutritional status of a cohort of 70 year olds living in western Jerusalem. A total of 605 persons were interviewed in their home regarding socioeconomic variables, education, self-assessed global health status, use of medicines, and activities of daily living (ADL). In the second stage, a subsample of 463 of the above attended an outpatient geriatric clinic where a medical history was taken and a physical examination, a cognitive test, a psychological profile, blood and urine tests, electrocardiogram, pulmonary function tests, and grip strength measurement performed. Most of the sample population lived at home. Twelve percent reported having severe financial problems. Approximately 14% exhibited some cognitive problems, 83% were totally independent in ADL, and only 15% were housebound with 2.5% being bedbound. Body mass index (BMI) of < 19 kg/m2 was found in 1.1% of the population, while obesity, defined as a BMI > 30 kg/m2, was found in 13.5% of males and 28.6% of females. Polypharmacy was prevalent. A quarter of the study population were taking three or more prescription drugs. Serum triglycerides were below the normal limit in 7.3% of males and 4.7% of females, while total serum cholesterol concentrations were low in 13.9% and 4.7% of males and females respectively. Serum albumin was found below the lower limit of normal (35 g/l) in 16.9% of females and 11.4% of males. The significance of these results, their relation to other nutritional surveys, and their implications for the future are discussed.
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PMID:The nutritional status of 70 year olds in Jerusalem. 881 70

Severely malnourished children afflicted by acute lymphoblastic leukemia (ALL), particularly in developing countries, have reduced tolerance to chemotherapy and a compromised prospect for survival. We investigated the prevalence and severity of alterations in growth and nutritional status in children with ALL from population-based referral areas in Canada. All children were treated with Dana-Farber Cancer Institute ALL Consortium protocols. First, the relative impact of cranial irradiation (CI) and chemotherapy on growth was studied in 116 children at diagnosis and at 6-month intervals during treatment. We observed a decline in height standard deviation (SD) score in the first year in all children, and a further decline in height SD score during the second year only in the children who received CI. Weight reduction occurred in the first year, but during the second year there was a disproportionate increase in weight compared with height, suggesting that children treated with ALL have a tendency toward obesity. Both chemotherapy and CI contribute to the altered growth observed in children treated for ALL. Second, intestinal functional integrity was assessed in 16 children during post-induction chemotherapy. Nutrient intake was adequate and there was minimal evidence of malabsorption: fat malabsorption occurred in only 1 child (after treatment-related pancreatitis), abnormal D-xylose absorption occurred in 2 children at 6 months of therapy (returning to normal 6 months later) and abnormal lactose absorption occurred in 4 children. Third, weight, height, whole body lean and fat mass measured by dual-energy X-ray absorptiometry and serum albumin were determined at diagnosis and at 6-month intervals throughout therapy in 19 children with ALL. Height SD scores decreased significantly during treatment. Serum albumin was abnormally low in 6/19 at diagnosis and 14/18 during intensive consolidation therapy. The mean change in the ratio of lean mass to total body weight showed a 5% reduction by 6 months of therapy. Body fat increased from a mean of 22% at diagnosis to 28% at completion of therapy. The majority of children treated for ALL thus have significant changes in nutritional status manifested by reductions in growth, alterations in lean and fat body mass and abnormally low serum proteins during intensive therapy.
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PMID:Growth and body composition in response to chemotherapy in children with acute lymphoblastic leukemia. 987 86

Dosages of anticancer drugs are usually calculated on the basis of a uniform standard, the body surface area (BSA). Although many physiological functions are proportionate to BSA, overall drug clearance is only partially related to this parameter. Consequently, following administration of equivalent drug dosages based on BSA, a wide variability in plasma drug concentrations can be found between patients, as a result of which some patients experience little toxicity while others may show severe toxic symptoms. A clear pharmacokinetic/pharmacodynamic correlation has been demonstrated for some anticancer drugs, and this relationship provides a background against which rational dose optimisation can be implemented for individual patients. The 3 strategies that can be employed for optimising dosage regimens, none based on BSA, are described and criticised. A priori adaptive dosage determination is based on the relative contribution of identifiable characteristics of patient, drug therapy and disease state that influence plasma drug concentrations; the dosage regimen is based on each patient's profile with regard to these characteristics. Although this approach is most successful with drugs whose clearance is closely tied to renal function, patient characteristics such age, obesity, serum albumin or hepatic function may be useful. The anticancer drug most closely identified with this approach is carboplatin, although dosage reduction strategies for etoposide, taxanes, anthracyclines, topotecan, oxazaphosphorines, vinca alkaloids or melphalan are advocated for patients with renal or hepatic dysfunction. The importance of pharmacogenetics for fluorouracil and mercaptopurine is also briefly discussed. The second approach consists of adaptive dosage adjustments during repetitive or continuous administration of a drug. It has been used for several years to administer methotrexate therapy and, more recently, it has been developed more fully and applied to continuous infusion of fluorouracil or etoposide. It was based, after determination of a target plasma concentration or area under the plasma drug concentration-time curve (AUC), on modification of the drug dosage during the cycle of chemotherapy or for the next cycle. Finally, the third approach of adaptive dosage adjustment with feedback control, based on population pharmacokinetics, with limited sampling strategy, may allow a feedback revision of the dosage following measurement of plasma drug concentration and comparison with the population previously studied. This approach is a theoretical strategy which has not, until now, been used prospectively in clinical oncology. For drugs such as anticancer agents with a very narrow therapeutic index, every effort should be made to minimise interpatient variability in drug exposure in order to maximise the benefit while keeping the risk of serious adverse effects at an acceptable level. This is particularly important when treatment is being given with curative intent.
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PMID:Practical treatment guide for dose individualisation in cancer chemotherapy. 987 90

We observed that some patients do not develop hypoalbuminemia despite the presence of massive proteinuria. To investigate whether the absence or presence of hypoalbuminemia could be a marker in the distinction between idiopathic focal segmental glomerulosclerosis (FSG) and FSG secondary to hyperfiltration, we reviewed all our patients with biopsy-proven FSG and persistent nephrotic-range proteinuria (>3.5 g/24 h). Patients who met these conditions were then separated into those with hypoalbuminemia (serum albumin level <3 g/dL; group I; n = 19) and those with normoalbuminemia (>3.5 g/24 h; group II; n = 18). All group I patients had nephrotic edema in contrast with the absence of edema in all group II patients. Serum cholesterol and triglyceride levels were significantly greater in group I. All group I patients had been diagnosed with idiopathic FSG. The diagnoses of group II patients were FSG secondary to massive obesity in eight patients (44%), vesicoureteral reflux in five patients (27%), and renal mass reduction in three patients (16%); only two patients (11%) in this group had idiopathic FSG. The case histories of 19 other patients with nephrotic-range proteinuria associated with hyperfiltering disorders (reflux nephropathy, massive obesity, renal mass reduction), but without renal biopsy, were also reviewed; despite massive proteinuria (5.8 +/- 3.1 g/24 h), serum albumin and total protein levels were always within normal values. In conclusion, patients with FSG secondary to hyperfiltration do not develop hypoalbuminemia or the other characteristic complications of nephrotic syndrome, despite the presence of massive proteinuria values.
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PMID:Absence of hypoalbuminemia despite massive proteinuria in focal segmental glomerulosclerosis secondary to hyperfiltration. 991 67

To evaluate a possible effect of peritoneal transport properties and dialysis dose on the physical development of children on chronic peritoneal dialysis, a cohort of 51 children was prospectively followed for 18 mo. Peritoneal transport characteristics were assessed by serial peritoneal equilibration tests (PET), dialysis efficacy by dialysate and residual renal clearance measurements, and growth and nutritional status by the longitudinal changes (delta) of height SD score (SDS), body mass index (BMI) SDS, and serum albumin. delta height SDS was negatively correlated with the creatinine equilibration rate observed in the initial PET (r = -0.31, P < 0.05). Multiple regression analysis confirmed the negative effect of the high transporter state (partial r2 = 0.07), and disclosed an additional positive effect of dialytic C(Cr) (partial r2 = 0.11) and a weak negative effect of daily dialysate volume (partial r2 = 0.04) on delta height SDS. delta BMI SDS was strongly age-dependent (r = -0.48, P < 0.001); while relative body mass gradually increased below 4 yr of age, it remained stable in older children. Positive changes in BMI SDS were associated with rapid PET creatinine equilibration rates (univariate r = 0.35, P < 0.05) and/or large dialysate volumes (multivariate partial r2 = 0.11), suggesting a role of dialytic glucose uptake in the development of obesity. The change in serum albumin concentrations was positively correlated with dialysate volume (partial r2 = 0.14), and negatively affected by dialytic protein losses (partial r2 = 0.06). In conclusion, the peritoneal transporter state is a weak but significant determinant of growth and body mass gain in children on chronic peritoneal dialysis. Rapid small solute equilibration contributes to impaired growth but enhanced acquisition of body mass. Dialytic small solute clearance has a weak positive effect on statural growth independent of the transporter state, but does not affect body mass gain.
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PMID:Peritoneal transport properties and dialysis dose affect growth and nutritional status in children on chronic peritoneal dialysis. Mid-European Pediatric Peritoneal Dialysis Study Group. 1044 47

Observational studies support the role of modifying lifestyle-related risk factors such as diet, physical activity and alcohol use in stroke prevention. For example, increased Na intake is associated with hypertension, and reduction in salt consumption may significantly lower blood pressure and may reduce stroke mortality. Moderately elevated homocysteine levels may be associated with stroke and are associated with deficiency of dietary intake of folate, vitamin B6 and vitamin B12. Consumption of a diet rich in fruits, vegetables, folate, K, Ca, Mg, dietary fibre, fish and milk may protect against stroke. Regular physical activity may also protect against stroke through its role in controlling various risk factors such as hypertension, diabetes mellitus and obesity. The role of fat intake as a risk factor for stroke remains uncertain, whereas the association between stroke and cholesterol has more convincingly been demonstrated by the recent intervention trials using statins. There is also evidence that a low serum albumin may be causally linked to stroke risk and outcome and that a significant number of stroke patients are undernourished on admission and their nutritional status deteriorates further whilst in hospital. Undernutrition is associated with increasing morbidity and mortality and nutritional supplements may have some beneficial effect on some outcome measures.
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PMID:Nutritional factors in stroke. 1096 Nov 55

Adipose tissue imposes problems in two-dimensional (2-D) analysis due to its extremely high content of fat. To improve protein separation detergents and chaotropes were varied in the IEF step. The most important factor for obtaining distinct spots in the 2-D gel was whether thiourea was included or not. Many high molecular weight spots became resolved by using thiourea, while no spots disappeared or showed inferior characteristics, thus approximately twice as many spots were possible to quantify. Hydrophobic indices were compared for a set of proteins that gave rise to sharper spots with proteins that were not improved on the use of thiourea. The comparison did not give any statistically significant difference between the two groups of proteins. One of the effects obtained by inclusion of thiourea was that the dominating protein, serum albumin, appeared as more condensed spots allowing other minor proteins to be detected. This work resulted in a protocol which greatly enhances the resolution of proteins in adipose tissue. A 2-D map of mouse white adipose tissue from epididymal fat pads was constructed in which 140 spots were identified by mass spectrometry. This work lays the ground for our further studies on white adipose tissue in metabolic diseases such as obesity and dyslipidemia.
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PMID:Thiourea enhances mapping of the proteome from murine white adipose tissue. 1150 6


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