Incidence of ventricular fibrillation during left coronary arteriography in pigs: comparison of a solution of the nonionic dimer iodixanol with solutions of five different nonionic monomers.

BACKGROUND: Solutions of iodine contrast media (CM) used for selective coronary arteriography (CA) should have minimal propensity to cause ventricular fibrillation (VF). Commonly used CM for CA are nonionic monomers or dimers. PURPOSE: To compare VF propensity of ready-to-use solutions of one nonionic dimer, iodixanol, and five nonionic monomers, iobitridol, iopamidol, iomeprol, iopromide, and ioversol. MATERIAL AND METHODS: Twenty milliliters of each CM was injected into the left coronary artery (LCA) through an inflated balloon catheter (0.5 ml/s) in 14 pigs; the longest period of injection was 40 s. If VF occurred before 40 s, the injection was stopped and the heart was defibrillated. After VF, there was a delay of 40 min before the next injection. Hemodynamic parameters and vector electrocardiography (VECG) were monitored. A CM with a lower frequency of VF and a longer period between start of injection and start of VF was considered to have a lower VF propensity. RESULTS: Following 14 injections, each of the five nonionic monomers caused 14 VF, whereas iodixanol caused three VF (P<0.01). When VF occurred after iodixanol, it occurred later than after the other CM (P<0.001). Iodixanol caused less prolongation in QRS time (P<0.01) and QTc time (P<0.05) than the other CM. Prolongations in QRS and QTc times caused by CM parallel the VF propensities of the CM. CONCLUSION: Ready-to-use solutions of the dimer iodixanol have lower VF propensity than solutions of the five monomeric CM. This is related to the fact that the solutions of the dimer iodixanol have lower osmolality, higher viscosity, and higher concentrations of NaCl and CaCl2 than solutions of the five monomers.

Determining 'true' glomerular filtration rate in healthy adults using infusion of inulin and comparing it with values obtained using other clearance techniques or prediction equations.

OBJECTIVE: To determine 'true' glomerular filtration rate (GFR) in healthy adults as renal clearance following infusion of inulin, and compare that result with those obtained using other markers and clearance techniques and with estimations of GFR using creatinine-based prediction equations. MATERIAL AND METHODS: Twenty healthy volunteers (11 females) with a median age of 27 years (range 19-36 years) received bolus doses of inulin and iohexol i.v. and 16 blood samples were taken after injection. Then, inulin and iohexol were infused to give stable plasma concentrations and blood and urine samples were collected. Residual bladder volume was estimated using ultrasound scanning. Plasma and urine concentrations of inulin and iohexol were determined using chromatography and resorcinol methods, respectively. Different methods of GFR determination were compared as well as four formulae for GFR estimation based on serum creatinine. RESULTS: 'True' GFR, i.e. renal clearance of inulin during its infusion, was a median of 117 ml/min/1.73 m2 (inter-quartile range 106-129 ml/min/1.73 m2). Similar values of GFR were obtained with renal clearance of iohexol during its infusion and also with plasma (body) clearance of inulin or iohexol following bolus injections and using 16 or five plasma samples. Endogenous creatinine clearance was higher (p<0.001) than true GFR (median 23 ml/min/1.73 m2). Plasma clearance of iohexol and inulin based on their concentrations in four blood samples underestimated their renal clearance considerably. All four creatinine-based formulae markedly underestimated renal inulin clearance. CONCLUSIONS: Plasma and renal clearance of iohexol and inulin were similar in healthy adults. Underestimation of GFR was noted when plasma clearance of iohexol and inulin was based on four but not five or more blood samples. Some prediction equations underestimate true GFR to such an extent that caution must be taken when using them to evaluate normal or high GFR values.

Histomorphological changes after renal X-ray arteriography using iodine and gadolinium contrast media in an ischemic porcine model.

BACKGROUND: Gadolinium contrast media (Gd-CM) are regarded as non-nephrotoxic or considerably less nephrotoxic than iodine contrast media (I-CM), and have therefore come to be used as a substitute for I-CM in patients with renal insufficiency in a variety of radiographic examinations. PURPOSE: To investigate renal histomorphological changes caused by Gd-CM in comparison with I-CM after renal X-ray arteriography in an ischemic porcine model,and to evaluate these changes in relation to the nephrotoxicity of the CM used. MATERIAL AND METHODS: Test solutions: gadopentetate, gadodiamide, iohexol, gadobutrol,iopromide, iodixanol, mannitol, and saline. The experiments were performed on 152 animals. Each pig was randomized to receive one test solution injected into the balloon occluded(10 min) right renal artery. The kidneys were evaluated histomorphologically.The severity of histomorphological changes was graded subjectively: 15 minimal, 25 mild, 35 moderate, and 4=marked. RESULTS: The main histological changes were 1) proximal tubular and glomerular necrosis,2) hemorrhage/congestion of the cortex, medulla, and glomeruli, 3) proximal tubular vacuolation, and 4) protein-filled tubules in the cortex and medulla. Necrosis and hemorrhage/congestion were more frequent after injections with gadopentetate, mannitol solution iso-osmotic to gadopentetate, and gadobutrol compared to all other groups(P<0.001). The degree of necrosis and hemorrhage/congestion was related to the degree of impairment of renal function, but inversely related to vacuolation and tubular protein filling. CONCLUSION: In ischemic porcine kidneys, the histomorphological changes caused by Gd-CM are similar to those caused by I-CM. Vacuolation appears to be independent of the osmolality and viscosity of the CM, and does not seem to be an indicator of renal impairment. "High-osmolal" Gd-CM are more nephrotoxic than "low- and iso-osmolal" I-CM when compared in equal volumes of concentrations, resulting in equal X-ray attenuation.

Contrast-medium-Induced nephropathy correlated to the ratio between dose in gram iodine and estimated GFR in ml/min.

PURPOSE: To suggest a more precise tool when assessing the risk of contrast-medium-induced nephropathy (CIN), i.e. the ratio between contrast medium (CM) dose expressed in grams of iodine (g-I) and estimated glomerular filtration rate in ml/min (eGFR; based on equations using serum-creatinine (s-Cr), weight, height, age, and/or sex), here named I-dose/GFR ratio. MATERIAL AND METHODS: A Medline search of published CIN investigations reporting mean eGFR and mean dose of low-osmolality CM (LOCM) identified 10 randomized controlled prophylactic and 2 cohort coronary investigations, and 3 randomized and 1 cohort computed tomographic (CT) investigation. From the randomized trials, data were collected only from the placebo or control arms, unless there was no significant difference between the control and test groups. The mean I-dose/GFR ratio of each study was correlated with the mean frequency of CIN-1 (s-Cr rise> or =44.2 micromol/l or > or =20-25%) and CIN-2 (oliguria or requiring dialysis). A maximum dose according to an I-dose/GFR ratio= 1 in patients with s-Cr ranging from 100 to 300 micromol/l was compared with that of CIGARROA'S formula and with a "European consensus" threshold published by the European Society of Urogenital Radiology, both using s-Cr alone to predict renal function. McCullough's formula was used to assess the risk of CIN requiring dialysis at an I-dose/GFR ratio= 1 with LOCM. RESULTS: The coronary investigations revealed a linear correlation with a correlation coefficient between the I-dose/GFR ratio and the frequency of CIN-1 and CIN-2 of 0.91 (P<0.001) and 0.84 (P=0.001), respectively. At a mean I-dose/GFR ratio= 1, the regression line indicated a 10%) risk of CIN-1 and a 1% risk of CIN-2. At a mean I-dose/ GFR ratio=3, the risk of CIN-1 and CIN-2 increased to about 50% and 15%, respectively. Pooled weighted data from the CT investigations revealed a 12% risk of CIN-1 at a mean I-dose/GFR ratio = 1.1 and no cases of CIN-2. The maximum CM dose according to an I-dose/GFR ratio= 1 was about 30-50% of that of both Cigarroa's formula and the "European consensus" in elderly low-weight individuals, while it was similar for middle-aged individuals weighing about 90 kg. McCullough's formula suggests that there will be an exponentially increasing risk of CIN requiring dialysis, but at an I-dose/GFR ratio= 1 and using LOCM it will not exceed 1% until GFR decreases below 30 ml/min in diabetics and below 20 ml/min in non-diabetics. CONCLUSION: Using the I-dose/GFR ratio may be a more expedient way of improving risk assessment of CIN than today's common practice of estimating CM dose from volume alone and renal function from s-Cr alone. Prospective studies based on individual patient data are encouraged to define the risk of CIN at various I-dose/GFR ratios and correlated to type of CM, examination, risk factors, etc.

Bone cement X-ray contrast media: a clinically relevant method of measuring their efficacy.

It is important to compare different contrast media used in bone cement according to their ability to attenuate X-rays and thereby produce image contrast between bone cement and its surroundings in clinical applications. The radiopacity of bone cement is often evaluated by making radiographs of cement in air at an X-ray tube voltage of 40 kV. We have developed a method for ranking contrast media in bone cement simulating the clinical situation, by (1) choosing the same X-ray tube voltage as used in clinical work, and (2) using a water phantom to imitate the effects of the patients' soft tissue on the X-ray photons. In clinical work it is desirable to have low radiation dose, but high image contrast. The voltage chosen is a compromise, because both dose and image contrast decrease with higher voltage. Three contrast media (ZrO(2), BaSO(4), and Iodixanol) have been compared for degree of "image contrast." Comparing 10 wt % contrast media samples at an X-ray tube voltage of 40 kV, ZrO(2) produced higher image contrast than the other media. However, at 80 kV, using a water phantom, the results were reversed, ZrO(2) produced lower image contrast than both BaSO(4) and Iodixanol. We conclude that evaluations of contrast media should be made with voltages and phantoms imitating the clinical application.

Contrast medium extravasation injury: guidelines for prevention and management.

Extravasation of contrast material is a well-recognized complication of contrast-enhanced imaging studies. The management of this complication is contentious; therefore, the Contrast Media Safety Committee of The European Society of Urogenital Radiology decided to review the literature and issue guidelines. A comprehensive literature search was carried out. The resulting report was discussed at the 8th European Symposium on Urogenital Radiology in Genoa, Italy. Automated power injection may result in extravasation of large volumes and may or can lead to severe tissue damage. Infants, young children and unconscious and debilitated patients are particularly at risk of extravasation during contrast media injection. Fortunately, most extravasations result in minimal swelling or erythema, with no long-term sequelae; however, severe skin necrosis and ulceration may occur. Large volumes of high osmolar contrast media are known to induce significant tissue damage. Compartment syndrome may be seen associated with extravasation of large volumes. Conservative management is often adequate, but in serious cases the advice of a plastic surgeon is recommended. Based on the review simple guidelines for prophylaxis and management of contrast medium extravasation injuries are proposed.

Biliary and total extrarenal clearance of inulin and iohexol in pigs. A source of error when determining gfr as body clearance.

Biliary clearance, total extrarenal clearance, body and renal clearance of inulin and iohexol were determined in 11 normal and 11 nephrectomized pigs. The biliary clearance of inulin, calculated as biliary excretion divided by the plasma concentration, was 0.04 and 0.01 ml min(-1) 10 kg(-1) and of iohexol 0.21 and 0.1 ml min(-1) 10 kg(-1), in normal, respectively, nephrectomized pigs (p < 0.05). The extrarenal clearance of inulin, calculated as body minus renal clearance, was 2.7 and 0.7 ml min(-1) 10 kg(-1) and of iohexol 3.7 and 0.7 ml min(-1) 10 kg(-1) in normal, respectively, nephrectomized pigs (p < 0.05). Some hours after injection of the markers their plasma concentrations were much higher in the nephrectomized pigs. This higher plasma concentration was not matched by an equally higher biliary excretion and therefore biliary clearance decreased. The smaller total extrarenal clearance in nephrectomized pigs, i.e. the overestimation of GFR when calculated as body clearance, indicates that this source of error decreases with decreasing renal function.

Committed to kids: an integrated, 4-level team approach to weight management in adolescents.

The integrated, 4-level approach of Committed to Kids is successful because of several factors: The sessions are designed to entertain the adolescents and promote initial success; The program features parent-training methods in short, interactive, educational sessions; In severely obese adolescents, the diet intervention results in noticeable weight loss that motivates the patient to continue; also, the improved exercise tolerance resulting from the weight loss promotes increased physical activity; and The program team provides consistent feedback-patients and their families receive results and updates every 3 months. Most importantly, the program is conducted in groups of families. The adolescent group dynamics and peer modeling are primary components of the successful management of obesity in youth.

Use of spiral CT and the contrast medium iohexol to determine in one session aortorenal morphology and the relative glomerular filtration rate of each kidney.

The aim of this study was to determine the relative glomerular filtration rate (GFR), i.e. the GFR of each kidney in percent of total GFR, by spiral CT. In 41 patients, who were part of a follow-up program after endoluminal stent grafting of aortic aneurysm, spiral CT with the contrast medium iohexol was used to evaluate the morphology of the aorta and kidneys. The opportunity was taken to utilize the already injected iohexol to determine the relative GFR with an extra CT sequence. In each patient two determinations were made, 6 or 12 months apart. The amount of a GFR marker accumulating in Bowman's space, tubuli, and renal pelvis within 2-3 min after i.v. injection, before any marker had left the kidney via the ureter, was defined as proportional to the GFR of that kidney. The renal accumulation of iohexol was obtained by spiral CT using 10-mm collimation and a table speed of 10 mm/s (pitch ratio 1:1) from the upper to the lower poles. The correlation coefficient between the relative GFR of each kidney determined at the first and second examination was excellent (r=0.99) with a median (range) difference of 1% (0-6%) of total GFR. The radiation dose calculated as the mean absorbed dose to the kidneys was 50 mGy and the effective dose 5 mSv. The morphology of aorta and kidneys and the relative GFR of each kidney can be determined in one session with spiral CT using iohexol as both angiographic contrast medium and as a GFR marker. It is also possible to take some plasma samples in the same session to determine iohexol concentration to calculate the body clearance of iohexol (or take plasma and urine samples to calculate the renal clearance of iohexol).

Tensile properties of a bone cement containing non-ionic contrast media.

The addition of contrast media such as BaSO4 or ZrO2 to bone cement has adverse effects in joint replacements, including third body wear and particle-induced bone resorption. Ground PMMA containing particles of the non-ionic water-soluble iodine-based X-ray contrast media, iohexol (IHX) and iodixanol (IDX), has, in bone tissue culture, shown less bone resorption than commercial cements. These water-soluble non-ceramic contrast media may change the mechanical properties of acrylic bone cement. The static mechanical properties of bone cement containing either IHX or IDX have been investigated. There was no significant difference in ultimate stress between Palacos R (with 15.0 wt % of ZrO2) and plain cement with 8.0 wt % of IHX or IDX with mass median diameter (MMD) of 15.0 or 16.0 microm, while strain to failure was higher for the latter (p < 0.02). The larger particles (15.0 or 16.0 microm) gave significantly higher (p < 0.001) ultimate tensile strengths and strains to failure than smaller sizes (2.4 or 3.6 microm). Decreasing the amount of IHX from 10.0 wt % to 6.0 wt % gave a higher ultimate tensile strength (p < 0.001) and strain to failure (p < 0.02). Scanning electron microscopy (SEM) showed the smaller contrast media particles attached to the surface of the polymer beads, which may prevent areas of the acrylate bead surface from participating in the polymerization. In conclusion, the mechanical properties of bone cement were influenced by the size and amount of contrast medium particles. By choosing the appropriate amount and size of particles of water-soluble non-ionic contrast media the mechanical properties of the new radio-opaque bone cement can be optimized, thus reaching and surpassing given regulatory standards.

Assessing residual renal function and efficiency of hemodialysis--an application for urographic contrast media.

BACKGROUND: In patients on hemodialysis with end-stage renal disease there is an increasing interest in measuring both residual renal function (RRF) and quantity and quality of dialysis because insufficient dialysis gives higher mortality. For that purpose we have measured clearances of two urographic iodine (I) contrast media (CM) with different molecular masses (iohexol 821 u and iodixanol 1, 550 u). These CM are filtered through glomeruli and dialysis membranes and have higher molecular masses than urea and creatinine and might represent the dialyzability of the hypothetic uremic toxins with a molecular mass of 300-5,000 u. METHODS: Thirteen patients (8 of them were anuric) immediately after hemodialysis received 15 ml iohexol (300 mg I/ml i.v.) and 2 weeks later in the same way 15 ml iodixanol (320 mg I/ml). Nine other patients (2 anuric) received CM after only one dialysis; 8 got iohexol and 1 got iodixanol. After the CM injections the iodine concentrations were measured with X-ray fluorescence in blood and, when available, urine during the following 2 days including both the start and end of the next dialysis. Eighteen patients after two dialysis sessions, 2 weeks apart, received 10 ml iohexol i.v., and a single blood sample was taken at the start of the next dialysis 2 days later to determine RRF alone. RESULTS: In the 10 anuric patients the extrarenal clearances (mean +/- SD) were 2.5 +/- 1.1 and 2.7 +/- 1.1 ml/min/1.73 m(2) for iohexol and iodixanol, respectively. In patients with RRF good correlations were demonstrated between body clearance, based on two blood samples, and renal clearance of CM. Good correlations (r(2) = 0.853 for iohexol, r(2) = 0.933 for iodixanol) were noted between two-sample and single-sample body clearances. Repeated single sample iohexol clearances gave a coefficient of variation of 15%. During dialysis the clearances of iohexol and iodixanol were, respectively, 69 +/- 16 and 58 +/- 11 ml/min/1.73 m(2) when calculated from a single-pool model (hemodialysis clearance of CM from plasma). A median increase (rebound) of CM concentrations in plasma 45 min dialysis was 8% for iodixanol and 18% for iohexol. When the CM concentration 45 min after dialysis was used, the clearance values were by 8-10% lower and represented the hemodialysis clearance of CM from the extracellular compartments. The dialysis eliminations of iohexol and iodixanol were similar to that of urea, measured as percentage reduction of serum levels during dialysis. CONCLUSIONS: A single injection of CM at the end of dialysis followed by a single blood sample at the start of the next dialysis gives total body clearance, i.e., an estimation of the RRF. An additional blood sample at the end of the next dialysis gives dialysis efficiency.

Recent advances in the treatment of childhood obesity.

The rapid increase in the prevalence of obesity in the last decade indicates a need for effective treatment programs. We conducted a short-term, repeated-measures, clinical-outcome trial in three groups of children and adolescents in two different locations. Two cohorts (n=34) were enrolled in a 36-wk multi-disciplinary weight-management program at the Children's Hospital of New Orleans. One cohort (n=16) was enrolled in a similar intervention at the General Clinical Research Center (GCRC) at the Medical Center of Louisiana for a 10-wk summer weight-loss program. Subjects were offered a protein-sparing modified fast (PSMF) diet (600-800 kcal/d; 2 g protein/kg body weight), followed by a balanced hypocaloric diet, and they participated in behavior-modification sessions and a moderate-intensity (45-55% volume of oxygen consumed at maximal effort [VO(2)max]), progressive exercise program. The following parameters were examined at baseline, 10 wk, and 36 wk (cohort 1 only): Weight, height, percentage of ideal body weight (%IBW), relative body fat (%fat), fat free body (FFB) mass, estimated VO(2)max mL/kg min(BW) [adjusted for body weight]), blood chemistries, lipid profiles (total cholesterol [TC], triglycerides [TG], low-density lipoprotein [LDL], high-density lipoprotein [HDL], and insulin-like growth factor-1 [IGF-1]). All three groups experienced significant decreases in weight, %IBW and %fat at 10 wk. The weight loss was maintained at 26 wk in cohorts 1 and 2, and at 36 wk in cohort 1. There were no significant decreases in height velocity during the study. In addition, measures of estimated VO(2)max mL/kg/min(BW) and IGF-1 parameters were significantly greater at 10 wk compared to baseline. Measures of TC, TG, and LDL were significantly lower at 10 wk, with no significant changes noted in HDL. We conclude that a multi-disciplinary weight-management program, including PSMF, behavior modification, and exercise, provides an effective method of treatment for obesity in children and adolescents. Long-term, randomized, and controlled clinical trials are needed to confirm the results of this preliminary, short-term observation.

A multidisciplinary approach to the treatment of childhood obesity.

Childhood obesity is a chronic disease that is associated with significant co-morbidity. Successful treatment and prevention of childhood obesity requires a multidisciplinary approach, including diet, nutrition education, behavior modification, and exercise. We studied 87 children (39 males, 48 females; aged 7-17 years) enrolled in a one-year multidisciplinary weight reduction program. Subjects were placed on a very low calorie/high protein diet, a moderate-intensity progressive exercise program, and behavior modification sessions for 10 weeks. Measures were taken at baseline 10 weeks, and 1 year. Significant anthropometric changes in weight, percent of ideal body weight, and percent body-fat were observed in all patients. We conclude that a multidisciplinary weight reduction program including diet, behavior modification, and exercise is an effective instrument to achieve weight loss in obese children and adolescents.

A cholesterol-lowering diet does not produce adverse psychological effects in children: three-year results from the dietary intervention study in children.

The Dietary Intervention Study in Children (DISC), a 2-arm, multicenter intervention study, examined the efficacy and safety of a diet lower in total fat, saturated fatty acids, and cholesterol than the typical American child's diet. A total of 663 8- to 10-year-old children with elevated low-density lipoprotein cholesterol levels were randomly assigned to either an intervention or a usual-care group. Intervention included group and individual counseling sessions to assist participants in adopting a dietary pattern containing 28% or less of calories from total fat (<8% as saturated fat, up to 9% as polyunsaturated fat, and 11% as monounsaturated fat) and dietary cholesterol intake of less than 75 mg/1,000 kcal. The dietary intervention reduced low-density lipoprotein cholesterol levels, and 3-year results showed no adverse effects for children in the intervention group in terms of academic functioning, psychological symptoms, or family functioning.

Maternal acceptability of a dietary intervention designed to lower children's intake of saturated fat and cholesterol: the Dietary Intervention Study in Children (DISC).

OBJECTIVE: This report examined the acceptability to mothers of a dietary educational and behavioral intervention for preadolescent children with elevated levels of serum low-density lipoprotein cholesterol (LDL-C) who were enrolled in the Dietary Intervention Study in Children (DISC). DESIGN: DISC is a randomized, controlled clinical trial. Subjects were randomly assigned to either an intervention or usual-care (control) group. SUBJECTS/SETTING: To be eligible for the study, participants were required to have the average of 2 fasting LDL-C values fall between the 80th and 98th sex-specific percentiles. Three hundred thirty-four 8-to 10-year-old children and their families were randomly assigned to an intervention group, and 329 were assigned to a usual-care (control) group. This study examined data from 232 subjects in the intervention group. Data were collected at 6 intervention sites around the United States. INTERVENTION: Those assigned to the intervention group participated in a multidisciplinary dietary intervention that included a series of group and individual sessions over a 3-year period. Children and their caretakers were taught to follow a nutritionally adequate diet that was low in total fat, saturated fat, and cholesterol and high in polyunsaturated fat. MAIN OUTCOME MEASURES: Three nonconsecutive 24-hour diet recalls were collected at baseline and at 1 year by trained and certified dietitians. A questionnaire designed to assess diet acceptability was administered at months 4, 8, 11, and 15. Demographic measures were collected at the onset of the study. STATISTICAL ANALYSIS PERFORMED: Statistical procedures included factor analysis and regression analysis. RESULTS: Regression analysis suggested that perceived effectiveness of the dietary intervention and mothers' having few concerns about disadvantages of the diet were significantly related to higher overall fat intake in children in one-parent families. Maternal willingness to implement the diet was significantly related to lower saturated fat intake. APPLICATIONS/CONCLUSIONS: In attempts to change eating behavior of children, interest and cooperation of the parents are essential to achieving successful results. These analyses further suggest that maternal acceptability translates into willingness to implement the diet and may facilitate changes that are associated with reduced saturated fat intake in children.

Clearance of iohexol, 51Cr-EDTA and endogenous creatinine for determination of glomerular filtration rate in pigs with reduced renal function: a comparison between different clearance techniques.

In order to simplify and/or improve determination of glomerular filtration rate (GFR) the clearances of iohexol, 51Cr-EDTA and endogenous creatinine were simultaneously determined with different techniques in 21 anesthetized landrace pigs. Their GFR had been reduced to about 1/3 or less of normal GFR. After an intravenous bolus of the GFR markers, their plasma concentration curves were followed for 6 hours with 16 plasma samples. A bladder catheter collected urine during six 60-min periods. The plasma clearance was calculated by dividing "dose of marker" with "area under the plasma concentration curve" (AUC) from the time of injection to infinity using a one- (Clprovisional) and a three-compartment (ClAUC-3comp) model. The renal clearance of iohexol and 51Cr-EDTA was calculated by dividing the amount of marker excreted in the urine in a period by AUC in the same period. The AUC was for iohexol and 51Cr-EDTA determined by integrating the total area in the period (Clren adv)-our reference method representing the "true" GFR and for creatinine determined by using the arithmetic mean of the plasma concentration of the marker at the start and at the end of the urine collection period (Clren simple). Renal clearance of creatinine was significantly lower than renal clearance of iohexol (p = 0.0019) and 51Cr-EDTA (p = 0.0001). There were no significant differences between the renal clearances (Clren adv) of iohexol and 51Cr-EDTA or between their plasma clearances (ClAUC-3comp). For iohexol the median overestimation of the "true" GFR with Clprovisional was higher when "early" plasma samples (30-120 min) were used (4.5 ml min-1 10 kg-1) than when late samples (180-360 min) were used (1.9 ml min-1 10 kg-1). Subtraction of the median extrarenal clearance (known from a study of nephrectomized pigs) from the plasma clearances (ClAUC-3comp) of iohexol and 51Cr-EDTA in pigs with reduced renal function decreased the median overestimation of the "true" GFR from 1.9 to 1.0 ml min-1 10 kg-1 with iohexol and from 1.7 to 0.9 ml min-1 10 kg-1 with 51Cr-EDTA. The plasma clearance technique may be improved in pigs with reduced GFR by (i) including a "late" plasma sample in three- and one-compartment models, which tends to increase the AUC; (ii) introducing a correction formula by normalizing the GFR values of the one-compartment model to those of the three-compartment model, thereby compensating for the rapid early changes in plasma concentration of marker after the bolus injection of the marker; or (iii) subtracting a median (or mean) extrarenal clearance of the marker in pigs from the plasma clearance [according to (i) or (ii)]. The plasma clearance one-compartment technique may be improved in pigs with various levels of GFR values by normalizing the plasma clearance values to the renal clearance values, thereby compensating for both the early changes in plasma concentration of marker and the extrarenal clearance of marker.

Feasibility of a clinic-based hypocaloric dietary intervention implemented in a school setting for obese children.

The objective of this study was to examine whether a protein-sparing modified fast diet and a hypocaloric balanced diet are effective in a clinic-based dietary intervention implemented in a school setting high-risk weight loss program for superobese (> or = 140% of their ideal body weight for height [IBW] children. A group of children from two suburban public schools in New Orleans, Louisiana were randomized to either dietary-intervention group and control group. Children were followed for 6 months. In the dietary-intervention-group, 12 of 44 superobese children [ages 8.8 to 13.4 years, weight 144% to 212% of IBW] volunteered to participate. In the control group, 7 of 19 superobese children [ages 9.4 to 12.9 years, weight 140% to 195% of IBW] volunteered to participate. During the first 9 weeks, 12 superobese children were placed on a 2520 to 3360 J (600 to 800 Cal) protein-sparing modified fast diet. Subsequently, the diets of all children were increased in a 3-month period 420 J (100 Cal) every 2 weeks until a 5040 J (1200 Cal) per day balanced diet was attained. In both groups, height and weight were obtained at baseline, 10 weeks, and 6 months; and biochemical measurements were performed at baseline and 6 months. At 6 months the 12 superobese children on protein-sparing modified fast diet had a significant weight loss from baseline (-5.6 +/- 7.1 kg, ANOVA p < 0.02); a significant decrease in percentage IBW (-24.3 +/- 20%, ANOVA p < 0.002); and had positive growth velocity Z-score (1.3 +/- 1.6, ANOVA p < 0.05). Six children were not superobese at 6 months. At 6 months eight of 12 children were active participants and 11 of 12 children were followed. Decrease in blood pressure, as well as, downward trends in serum lipids were observed at 6 months. No clinical complications were observed. At 6 months, the 7 control superobese children, when compared with baseline had gained weight (2.8 +/- 3.1 kg, ANOVA p < 0.008); but had no significant change in percentage IBW (-0.3 +/- 5.9%, ANOVA p = 0.61); and had no changes in growth velocity Z-score (0.1 +/- 1.3, ANOVA p = 0.83). These children did not have any change in blood pressure and an upward trend in serum lipids were observed at 6 months. Protein-sparing modified fast diet and a hypocaloric balanced diet appear to be effective in a group of superobese-school-age children in a medically supervised clinic-based program implemented in a school setting over a 6-month period. The efforts of committed clinic staffs, school officials, peers, and family involvement were crucial to the success of this intervention program in promoting and maintaining weight loss over a 6-month period. Further research with a specific comparison of the hypocaloric diets with longer follow-up periods in the school setting is necessary. In the meantime, these diets should be used only with close medical supervision.

Clearance of iohexol, chromium-51-ethylenediaminetetraacetic acid, and creatinine for determining the glomerular filtration rate in pigs with normal renal function: comparison of different clearance techniques.

RATIONALE AND OBJECTIVES: We wanted to improve determination of the glomerular filtration rate (GFR) with plasma clearance techniques because the alternative-renal clearance techniques-may involve inaccurate urine sampling or risk of urinary tract infection when bladder catheterization becomes necessary. Therefore, we compared the renal and plasma clearances of iohexol and chromium-51-ethylenediaminetetraacetic acid (51Cr-EDTA), as well as endogenous creatinine clearance, in 19 normal pigs using different techniques. METHODS: After an intravenous bolus injection of the GFR markers, 16 plasma samples were used to plot the marker concentrations versus time for 4.5 hr. Urine was collected during nine 30-min periods. Plasma clearance was calculated by dividing the dose of marker with the area under the plasma concentration curve (AUC) from the time of injection to infinity using one-compartment (ClAUC-slope) and three-compartment (ClAUC-3comp) models. The renal clearance was calculated by dividing the amount of marker excreted in the urine in a period with the AUC in the same period. This AUC was determined by integrating the total area in the period (Clren adv)--our reference method representing the "true" GFR--or by using the arithmetic mean of the plasma concentrations of the marker at the beginning and end of the urine collection period (Clren simple). Creatinine clearance was determined according to Clren simple. RESULTS: Renal clearances of iohexol and 51Cr-EDTA were significantly higher than creatinine clearance (P = .0002). There was no significant difference between the renal clearances of iohexol and 51Cr-EDTA or between their plasma clearances. The two mathematical methods of calculating the renal clearance of iohexol were highly correlated (rs = .99), as were the two methods of calculating its plasma clearance (rs = .95). Because of the extrarenal clearance of the markers, the plasma clearance methods for iohexol and 51Cr-EDTA always overestimated the true GFR. ClAUC-3comp was the method closest to the true GFR. For iohexol, the median overestimation of the GFR was higher with ClAUC-slope when early plasma samples (30-120 min) after injection of the marker were used (5.5 ml.min-1.10 kg-1) than when late samples (180-270 min) were used (4.0 ml.min-1.10 kg-1). After subtracting the median extrarenal clearances of iohexol and 51Cr-EDTA (previously determined in nephrectomized pigs) from their plasma clearances (ClAUC-3comp), the median overestimation of the true GFR was reduced from 2.0 to 1.1 ml.min-1.10 kg-1 with iohexol and from 2.1 to 1.3 ml.min-1.10 kg-1 with 51Cr-EDTA. CONCLUSION: GFR determination with plasma clearance techniques can be improved in three- and one-compartment models by taking late plasma samples and by subtracting the extrarenal plasma clearance of the species. One-compartment models can be improved by determining a correction formula in the species for the early parts of the decay curve of the plasma concentration of the marker.