Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
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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

Body composition determines body water content (the fraction body water/body weight). With developing obesity, body weight and body water increase, but body water content decreases. The anthropometric formulas for urea volume (body water) for Kt/V computations in nonamputated peritoneal dialysis subjects reflect this fundamental rule of body composition. However, the use of uncorrected anthropometric formulas in amputees provides body water content estimates inconsistent with the estimates of body composition obtained from nutritional assessment. Corrected estimates of urea volume can be obtained in three steps: (1) The non-amputated weight at the same body composition is computed by dividing the weight at the urea kinetic study (postamputation) by (1-the fractional weight loss from the amputation); (2) body water and body water content at this nonamputated weight are obtained from the appropriate anthropometric formula; (3) at the time of the urea kinetic study, post-amputation, body water is equal to the estimate of body water content obtained from step 2 times the body weight at the urea kinetic study. The corrected estimates of urea volume provide body water content values agreeing with the estimates from nutritional assessment.
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PMID:Estimating urea volume in amputees on peritoneal dialysis by modified anthropometric formulas. 886 89

The study purpose was to determine the following in a large sample of hospitalized patients: (1) the prevalence of hyperuricemia, (2) the association of hyperuricemia with other metabolic disorders, and (3) the factors independently predicting hyperuricemia. Five hundred adult patients (250 men and 250 women) were randomly selected from those admitted as inpatients over a period of 5 months. In all patients, body mass index (BMI), blood pressure, and serum glucose, lipid, creatinine, urea nitrogen, and urate concentrations were measured. The presence of diseases or use of medications known to affect serum urate levels were recorded. The mean level of serum urate was 5.6 mg/dL in the whole sample, 6.0 mg/dL in men and 5.3 mg/dL in women (P = .003, men v women). The prevalence of hyperuricemia was 27.6% (28.8% and 26.4% in men v women, P = nonsignificant). A definite or probable secondary hyperuricemia was found in 87.7% of the subjects. Hyperuricemia was rarely isolated (21%), whereas it was frequently associated with hypertension (60.1%), hyperlipidemia (31.2%), diabetes (28.3%), and obesity (21.7%). In 26.8% of the subjects, hyperuricemia was associated with two metabolic disorders, in 13.8% with three, and in 2.9% with four. Multiple metabolic disorders (three to four) were found in 16.7% of subjects with hyperuricemia. Serum urate levels progressively increased across a range of subjects from those without diabetes, hyperlipidemia, hypertension, or obesity to those with one, two, or a greater number of associated metabolic abnormalities. Multiple stepwise regression analysis showed that 43% of serum urate variability was explained by urea nitrogen levels, triglyceride levels, diuretic therapy, the inverse of creatinine (as an index linearly related to creatinine clearance), and BMI. These results indicate that in hospitalized subjects, hyperuricemia is (1) frequent, (2) a secondary phenomenon in most cases, and (3) frequently associated with other metabolic disorders. The major predictors of high serum urate levels are BMI, triglycerides, parameters of renal function, and use of diuretics. These variables explain a large proportion of serum urate variability.
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PMID:Serum uric acid and related factors in 500 hospitalized subjects. 896 92

The effect of gender and degree of obesity on the size indicators V, used to normalize urea clearance (Kt/Vur), and body surface area (BSA), used to normalize creatinine clearance (Ccr), in peritoneal dialysis was studied by: (1) mathematical comparison of the formulae used to estimate V (Watson and Hume) with the Dubois formula used to estimate BSA in peritoneal dialysis; and (2) comparison of percent deviation of BSA (delta BSA%) and V (delta V%) from ideal weight estimates in 933 clearance studies performed in actual patients (555 in men and 378 in women on continuous ambulatory peritoneal dialysis). V was estimated by the Watson formulae and BSA by the Dubois formula in these studies. delta BSA% and delta V% were stratified in 10% increments in deviation of body weight from ideal (delta W%) in these studies. Mathematically, the relationship between V and BSA is not linear. In the same subject, as obesity develops (delta W% increases) and BSA increases in a linear manner, V increases exponentially. In addition, there are substantial differences in the relationship between V and BSA caused by gender. For the same height and BSA, men have a larger V than women. In the clearance studies performed in actual continuous ambulatory peritoneal dialysis patients, the difference between delta V% and delta BSA% increased significantly (P < 0.0001) from the wasted to the obese subjects by one-way ANOVA in both men and women. Normalization of urea and creatinine clearances by different size indicators creates two types of mathematical distortion in the relationship between the two clearances. One distortion is caused by the degree of obesity. The second distortion is caused by gender. Use of the same size indicator to normalize both urea and creatinine clearances would eliminate these distortions.
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PMID:Gender, degree of obesity, and discrepancy between urea and creatinine clearance in peritoneal dialysis. 951 14

Growth of children during maintenance hemodialysis has been reported to be uniformly poor, with a mean annual loss of 0.4 to 0.8 SD in height. We adopted an intensive program of closely monitored energy and protein intake with dialysis urea clearances exceeding conventional recommendations. Twelve prepubertal or early pubertal children (aged 7 months to 14 years) were monitored for an average of 2.2 years (range 4 to 81 months) while receiving maintenance hemodialysis. These children received an average of 90.6% and 155.9% of their recommended energy and protein nutritional intake, respectively. With a prescribed urea clearance of 5 mL/kg/min, we achieved a mean single treatment urea clearance normalized for total body water of 2.00, a urea reduction ratio of 84.7%, and an average time of hemodialysis of 14.8 h/wk, all well beyond current guidelines. Over the course of dialysis treatment, the improvement in height SD score was+0.31 SD/y (+0.32 excluding the 2 children treated with recombinant human growth hormone). Normal growth was achieved without overt obesity and was associated with normal pubertal growth spurt. These findings suggest that the combination of increased dialysis and adequate nutrition can promote normal growth in children treated with long-term hemodialysis.
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PMID:Growth during maintenance hemodialysis: impact of enhanced nutrition and clearance. 1019 Sep 22

ZD7114, [(S)-4-[2-(2-hydroxy-3 phenoxypropylamine)ethoxy]-N-(2-methoxyethyl) phenoxyacetamide], and ZD2079, [(R)-N-(2-[4- (carboxymethyl)phenoxy]ethyl)-N-(beta-hydroxyphenethyl)ammonium chloride], are beta 3-adrenoceptor stimulants with selectivity for brown adipose tissue. ZD7144 is the hydrochloride salt of the S-enantiomer of the racemic amide ZD2079. They were developed as potential novel treatments for obesity and non-insulin-dependent diabetes mellitus. Male and female rats were dosed separately by gavage for a minimum of 28 days with 0, 10, 50, and 500 mg/kg/day of ZD7114 or with 0, 10, 30, and 150 mg/kg/day of ZD2079. Two further groups of male and female rats were dosed with 0 and 500 mg/kg/day of ZD7114 for 28 days and were then allowed a 6-wk, undosed withdrawal period. At high doses, both compounds caused urinary tract toxicity, which primarily affected the distal tubules and collecting ducts of the kidney via tubular necrosis. They also caused ureteric inflammation, cystitis, and accumulation of crystalline inclusions throughout the urinary tract. As a result of urinary tract toxicity, affected animals from one or both studies showed reduced red blood cell indices, lower platelet counts, and higher white cell counts. Blood chemistry revealed lower plasma concentrations of glucose (7.28 +/- 1.37 compared to 8.11 +/- 0.65 for the control) and total protein (63.42 +/- 3.65 compared to 69.17 +/- 3.24 for the control) and increased plasma urea (37.15 +/- 19.96 compared to 8.09 +/- 0.87 for the control). Urinalysis showed an increase in the number of crystals, blood, and protein. In the urinary tract, the severe crystalluria with accumulation of crystalline material indicated that this may have a role in the etiology of the target organ toxicity. Poor solubility of the compounds at normal urinary pH was considered a possible mechanism for the crystalluria.
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PMID:Urinary tract toxicity in rats following administration of beta 3-adrenoceptor agonists. 1020 80

Nosocomial infections are one of the most feared complications after open heart surgery. A large retrospective study was conducted to evaluate the nature and scope of the problem. Between 1992 and 1998, 9352 patients who had undergone open heart surgery were evaluated. Bloodstream infections, pneumonia, and deep sternal wound infections were included. Univariate and logistic regression analyses were conducted to identify the high-risk patients that were likely to become infected. Three hundred forty-six infections in 276 patients were diagnosed. Age, preoperative albumin level, banked blood requirement, duration of operation, diabetes mellitus, previous open heart surgery, moderate or severe pericardial adhesions, obesity, postoperative low cardiac output, and postoperative cerebrovascular accident were found to be significant in univariate and logistic regression analyses for infectious outcome. Univariate analysis also revealed additional significant factors: fresh frozen plasma requirement, duration of cardiopulmonary bypass and cross-clamp, preoperative high levels of blood urea and glucose, presence of occlusive peripheral arterial disease, preoperative history of hypertension, and nasal carriage of Staphylococcus aureus. Methicillin resistant S. aureus was involved in 58.4% of the infections. Risk factors should be individualized for patients and every effort should be carried out to minimize infectious outcome.
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PMID:Bloodstream, respiratory, and deep surgical wound infections after open heart surgery. 1022 80

The metabolic differences in vitro between genetic and dietary obese rats in the uptake of ammonium and amino acids by the liver and their use for ureogenesis have been assayed using hepatocytes isolated from Lean, Obese Zucker (Genetic obese) rats and Dietary obese rats. The hepatocytes of genetic obese animals took up more ammonium and produced higher amounts of urea from ammonium and alanine than those of lean and dietary obese groups (2 and 5 times more respectively). In the lean and dietary obese groups urea synthesis accounted for almost all the nitrogen taken up as ammonium. Thus, dietary and genetic obesity show a widely different handling of nitrogen, and the genetic obese rats need to break down protein to maintain their hepatocyte function.
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PMID:Ammonium uptake and urea production in hepatocytes from lean and obese Zucker rats. 1056 96

Despite extensive experimental studies on total starvation, many of the findings relating to protein, fat (plus ketone body), and carbohydrate metabolism remain confusing, although they become more consistent when considered in relation to the degree of initial obesity. During prolonged starvation, protein loss and percent energy derived from protein oxidation are 2- to 3-fold less in the obese than in the lean; percent urine N excreted as urea is 2-fold less in the obese; and the contribution of protein to net glucose production is only about half in the obese compared to lean subjects. During short-term starvation (first few days) the following differences are reported: hyperketonaemia is typically 2-fold greater in lean subjects, but associated with a 2-fold lower uptake of ketone bodies by forearm muscle; glucose tolerance becomes impaired more in lean subjects; and both protein turnover and leucine oxidation increase in the lean, but may show no significant change in the obese. It is no longer acceptable to describe the metabolic response to starvation as a single typical response. The differences between lean and obese subjects have important physiological implications, some of which are of obvious relevance to survival.
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PMID:Differences in fat, carbohydrate, and protein metabolism between lean and obese subjects undergoing total starvation. 1106 60

To determine possible genetic influences on the steady-state concentrations of several key transcription factor transcripts and the transcript concentrations for adipocyte-characteristic proteins, young, genetically obese and lean pigs were given ad libitum access or feed or were restrictively fed at 50% of ad libitum intake for 5 wk. Obese pigs were smaller and fatter than lean pigs, whether intake was ad libitum or restrictive. Plasma protein, albumin, and cholesterol concentrations were greater in obese than in lean pigs. Plasma NEFA, blood urea nitrogen, triacylglycerols, and postprandial glucose and insulin concentrations were less (P < .02) in pigs fed restrictively than in pigs with ad libitum access to feed, regardless of genetic group. The adipose tissue glucose transporter 4, fatty acid synthase, and leptin transcript concentrations were greater (P < .05) in obese than in lean pigs. The CCAAT/enhancer binding proteins beta and alpha, adipocyte fatty acid binding protein, hormone-sensitive lipase, and the beta1-adrenergic receptor transcript concentrations tended (P < . 10) to be greater in adipose tissue from obese than in that from lean pigs. Several other transcripts were numerically greater in obese than in lean pigs. The data collectively suggest that messenger RNA concentration for several adipose tissue proteins is a contributing factor to the excess fat deposition in these obese pigs. Restricted feeding did not change the concentration of any transcript except that for adipocyte fatty acid binding protein, which was reduced. The accretion of fat was markedly reduced in the restrictively fed pigs, but this diminution does not seem to be regulated by modulation of messenger RNA concentration.
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PMID:Effect of feed restriction on adipose tissue transcript concentrations in genetically lean and obese pigs. 1078 83


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