Association between glomerular filtration rate and extracellular fluid volume in normal subjects and patients with renal impairment

The aim of the study was to determine the extent to which glomerular filtration rate (GFR) measured with one filtration marker is associated with extracellular fluid volume (ECV) measured independently with another. Cr-51-EDTA and iohexol were injected simultaneously into opposite arms in 20 normal volunteers and 60 patients. Cubital samples taken bilaterally at 20, 40, 60, 120, 180 and 240 min were assayed for marker injected contralaterally. GFR was scaled to body surface area of 1.73 m(2) (GFR/BSA). GFR was also expressed as marker transit time (GFR/ECV) and ECV as the product of marker transit time and GFR/BSA. In normal subjects, changes between fasting and non-fasting ECV/BSA correlated positively with changes in GFR/BSA, but not GFR/ECV. GFR/BSA and GFR/ECV correlated positively (regression slope approximately 4 ml.min(-1).litre(-1)) and negatively (-2.7 ml x min(-1) x litre(-1)), respectively, with ECV/BSA. The difference, 6.7 ml x min(-1) x litre(-1), expressed as a fraction of average scaled GFR ( approximately 90 ml x min(-1)) is close to the reciprocal of average ECV/BSA (13.5 litres.1.73 m(-2)), consistent with the expected slope of the regression on ECV/BSA of the difference-to-average ratio of GFR/BSA and GFR/ECV. In contrast, in 29 patients with impaired GFR (estimated from plasma creatinine), ECV/BSA correlated inversely with GFR/ECV (slope approximately -5 ml x min(-1) x litre(-1)) but showed no relation with GFR/BSA. We conclude that in normal subjects GFR/BSA increases in response to increasing ECV/BSA, but the increase is not proportionate, leading to a weak inverse association between GFR/ECV and ECV/BSA. When ECV is expanded in patients with renal impairment, however, there is no GFR response, leading to a reduction in GFR/ECV.     

The pharmacokinetics of high-dose carboplatin in pediatric patients with cancer.

Carboplatin disposition was studied in 18 pediatric patients with cancer over a dosage range of 400 to 700 mg/m2 given on an alternate-day schedule (total doses of 1200 to 2100 mg/m2) with high-dose etoposide. Median age was 7.7 years, hepatic functions were normal, and serum creatinine levels were less than or equal to 1.0 mg/dl. Carboplatin pharmacokinetics were determined by atomic absorption spectroscopy. Median pharmacokinetic parameters for ultrafilterable platinum were as follows: clearance 45.8 ml/min/m2 (range, 25.5 to 65.3 ml/min/m2) and a terminal half-life of 3.6 hours (range, 2.1 to 14.2 hours). Carboplatin clearance (CL) values and volume of distribution (VC) were highly correlated to body size (CL = 55 x Body surface area in [BSA, in square meters] - 6.7, r2 = 0.73; VC = 5 x BSA [in square meters] + 0.26, r2 = 0.69). However, carboplatin doses normalized to BSA still resulted in twofold to threefold variability in area under the concentration-time curve. Carboplatin CL was significantly lower in those subjects (n = 9) who had previously received cumulative cisplatin doses of greater than or equal to 960 mg/m2 (p less than 0.05) but was not influenced by age, gender, or diagnosis.     

Physiological response to the ambulatory performance of hand-rim and arm-crank propulsion systems

Two types of propulsion systems-the hand rim (HR) and the arm crank (AC)-are commonly used in wheelchair ambulation. The purpose of this study was to investigate the physiological response of the two propulsion systems under actual locomotive condition by the actual users. The energetics of locomotion manual wheelchair (HR propulsion) and arm-propelled three-wheeled chairs (AC-propelled) at their free chosen speed (FCS) were studied and compared. Thirty-four male subjects with dysfunctioning lower limbs; 17 manual wheelchair users and 17 arm-propelled three-wheeled chairs regular users volunteered to participate in the study. Speed (m.min-1), oxygen uptake (1 x min(-1)) and heart rate (b x min(-1)) were monitored during steady-state ambulation at FCS for 5 min. Oxygen consumption (VO2, ml x kg(-1) min(-1)), oxygen cost (VO2, ml x kg(-1) m(-1)), net locomotive energy cost (kcal kg(-1) km(-1)) and physiological cost index (b x m(-1)) were derived. The FCS of the AC propelled device is remarkably higher than the HR system, and the magnitude of the physiological variables of the AC propulsion system was significantly lower (p<0.001) in relation to the HR propulsion system, as revealed from the results of t test for two sample means at a significance level p=0.001. It can be inferred from the result that the AC propulsion system could be used for long distance rides with a higher speed required for outdoor ambulation and that the HR propulsion system is suitable only for indoor use, because of its excellent maneuverability where short-duration low-velocity ambulation is required.     

Indexed glomerular filtration rate as a function of age and body size

The conventional way in which to scale or index a measurement of glomerular filtration rate (GFR) is to express it in relation to body surface area (BSA). However, BSA may not be appropriate for infants and children because, as individuals increase in size, their relative BSA decreases. Several other whole-body variables have been suggested as alternatives, including extracellular fluid volume (vECF). The purpose of the present study was to compare BSA and vECF as variables against which to index GFR, and in particular to look at this comparison in children versus adults. A total of 130 patients (age range 1-80 years; 40 patients <12 years) undergoing clinically indicated routine measurement of GFR using the bolus-injection single-compartment technique were included in the study. GFR was measured as the plasma clearance of [(51)Cr]EDTA as assessed from three peripheral venous blood samples taken between 2 and 4 h after injection of [(51)Cr]EDTA. Volume of distribution (V(d)) was obtained by extrapolation of the clearance curve to zero time. GFR was scaled to a BSA of 1.73 m(2). GFR and GFR/1.73 m(2) were corrected to account for the assumption of a single compartment. The rate constant of the exponential between 2 and 4 h was also corrected to give GFR/litre ECF. GFR and GFR/1.73 m(2) were both divided by GFR/litre ECF, to give vECF and vECF/1.73 m(2) respectively. Weight per unit BSA increases as a linear function of BSA. vECF is always less than V(d), on average by about 30%. vECF increased as an exponential function of BSA and as a linear function of body weight. vECF/70 kg body weight was higher in children (16. 2+/-3 litres) than adults (13.4+/-2.3 litres), but vECF/1.73 m(2) was lower in children (9.7+/-1.7 litres) compared with adults (12. 4+/-2 litres). vECV/1.73 m(2) increased as a function of both age and BSA, but vECF/kg decreased. GFR/12.5 litres vECF was higher than GFR/1.73 m(2) in children, but these values were similar in adults, with the ratio of these two forms of indexed GFR falling significantly with both age and BSA. Although this was not a normal population, but one with a wide range of renal function, GFR/vECF showed a strong inverse association with age, whereas for GFR/BSA the association was weak. In conclusion, these data provide further evidence that vECF is more valid physiologically for indexing GFR than is BSA, especially in children. Nevertheless, a GFR measurement in a child should ideally be expressed as a percentage of normal for that child's age. However, such normal values are not yet available.     

Can Current Minute Ventilation Rate Adaptive Pacemakers Provide Appropriate Chronotropic Response in Pediatric Patients?

Since children have different activity patterns and exercise responses, uncertainty exists as to whether minute ventilation (MV) sensors designed for adults provide adequate chronotropic response in pediatrics. In particular, high respiratory rates (RR > 48 breaths/min), which are characteristic of the ventilatory response to exercise in children, cannot be sensed by MV rate responsive pacemakers. The purpose of this study was to evaluate the MV sensor rate response of the Medtronic Kappa 400 using exercise data from healthy children in a computer simulation of its rate response algorithm. Thirty-eight healthy children, ages 6-14, underwent a treadmill maximal exercise test. Subjects were divided based on body surface area (BSA) and MV rate response parameters were selected. Respiratory rates and tidal volumes were entered into the Kappa 400 rate response algorithm to calculate sensor-driven rates. Intrinsic heart rate (HR), oxygen uptake, and sensor-driven rates were normalized to HR reserve (HRR), metabolic reserve (MR), and sensor-driven reserve to compare across groups. Linear regression analysis among sensor-driven rate reserve, HRR, and MR was performed as described by Wilkoff. The mean slopes (+/- SD) of the relationships between the sensor-driven rate reserve and HRR were 1.06 +/- 0.34, 1.07 +/- 0.28, and 1.01 +/- 0.19 for children with BSA < 1.10 m2, 1.10 < BSA < 1.40 m2, and BSA > 1.40 m2, respectively. High correlations were found between sensor-drive rates and HR responses and between sensor-drive rates and MV throughout exercise. No significant differences were noted between sensor-drive rates and HR using the Wilkoff model. From this study the authors conclude that: (1) MV is a good physiological parameter to control heart rate and (2) simulated sensor-driven rates closely match intrinsic HRs during exercise in healthy children, which supports the appropriateness of clinical validation in pediatric pacemaker patients.     

Gender differences in normalized clearances in CAPD: role of body size and normalizing parameters.

OBJECTIVE: To compare raw (not normalized) and normalized urea and creatinine clearances between women and men on continuous ambulatory peritoneal dialysis (CAPD). To study whether potential gender differences are due to the normalization process. DESIGN: Retrospective analysis of clearance studies. SETTING: Dialysis units of four academic medical centers. PARTICIPANTS: The study included 302 subjects (135 women and 167 men) on CAPD with four daily exchanges and a 2-L exchange volume. INTERVENTION: Measurement of urea and creatinine clearances (261 in women, 352 in men) by standard methods. Body water (the volume of distribution, V, for both urea and creatinine) was estimated by the Watson anthropometric formulas. MAIN OUTCOME MEASURES: Comparison of raw and normalized clearances between women and men. Urea clearance was normalized by V (Kt/Vur), while creatinine clearances was normalized by both V (Kt/Vcr) and body surface area (BSA) (Ccr). RESULTS: Mean values of weekly total (peritoneal plus renal) raw clearances were higher in men (urea clearance: women 67.1 L, men 77.4 L; Ccr: women 61.7 L, men 78.3 L). Raw renal clearances were higher in men, while raw peritoneal clearances were comparable. Mean weekly total Kt/Vur was higher in women (2.19 vs 1.94 in men), mean weekly total Kt/Vcr did not differ between the genders (women 2.01, men 1.95), while mean weekly Ccr was higher in men (73.0 vs 64.7 L/1.73 m2 in women). When clearances differed, the differences were significant at p < 0.001. Men had greater height and weight, while women had greater body mass index. On the average, V in men exceeded V in women by 31%, while BSA in men exceeded BSA in women by only 12%. CONCLUSIONS: Normalization of clearances by V creates relatively higher clearance values in women, while normalization by BSA creates relatively higher clearance values in men. Thus the normalization process may create artificial differences in the normalized clearances between genders.     

High-resolution two-dimensional echocardiography improves the quantification of left ventricular function.

It is not clear if newer echo technology prevents underestimation of ejection fraction in comparison with cineventriculography (CVG). Before undergoing CVG, 48 patients were studied with state-of-the-art, high-resolution two-dimensional echocardiography with a 3.5 MHz transducer, 96 crystals, and digital storing (slow motion and cine-loop). These data are compared with results published by us in 1983 (37 patients). Volumes were calculated using the biplane method of discs in a single area length. Exclusion criteria in 1990 were poor two-dimensional echocardiography quality (n = 6) and extra-systole during CVG (n = 4). The difference between the mean values of the angiography and echocardiography data in the new study (1990) were 4.7 ml/m2/body surface area (BSA) for the end-diastolic volume, 0.1 ml/m2 for the end-systolic volume, and 1.5% for the ejection fraction (all NS). The mean difference between both methods in the old study (1983) were -39.1 ml/m2/BSA (p less than 0.001) for end-diastolic volume, -17.4 ml/m2 (p less than 0.001) for end-systolic volume, and -7.2% for ejection fraction (p less than 0.001). The regression equation for determination of ejection fraction was y = 0.606x + 13, r = 0.803 for the old study, and y = 0.935x + 2.5; r = 0.935 for the new study. These results indicate that state-of-the-art, high-resolution two-dimensional echocardiography prevents the systematic underestimation of left ventricular volume and ejection fraction, most likely because of better delineation of endocardium in end-systole.     

Anti-CEA immunoscintigraphy in postoperative follow-up of tumor patients. Differentiated use of various monoclonal antibody preparations

The sensitivity of immunoscintigraphy (ISC) with monoclonal antibodies (Mab) depends on the Mab type, the radiophysical properties of the isotope, the labeling method and the tumor localization. We investigated 38 studies with three different Anti-CEA Mab (In111/I131 BW 431, n = 12; I131 IMACIS-1, n = 11; Tc99m BW 431/26, n = 15) in 35 postoperative tumor patients (31 colorectal, 1 gastric, 2 breast and 1 pancreas cancer) with a total of 62 tumor manifestations. Planar ISC was used in all studies. A dual isotope technique with Tc99m-colloid was applied for imaging of liver metastases in the In111/I131 BW 431/31 and I131 IMACIS-1 studies. Whereas the global sensitivity, ranging from 64-73%, was comparable, the different physiological properties of the Mab preparations caused marked differences in the imaging capabilities of certain tumor localizations, especially in the liver. All Mab underestimated the extent of liver involvement, however, the highest regional sensitivity (75%) was found with the I131 IMACIS-1. In contrast, Mab with the highest physiological liver uptake (In111 BW 431/31, Tc99m BW 431/26) imaged liver metastases in most cases unspecifically as cold spot, yielding a sensitivity of 0-9%. No differences between the Mab were seen in the regional sensitivity with respect to lung metastases, which ranged between 33-40%. All tested Mab showed a high sensitivity in imaging local recurrences ranging between 50% for the I131 IMACIS-1 and 100% for the Tc99m BW 431/26. We conclude, that in postoperative tumor patients anti-CEA ISC with Tc99m BW 431/26 is the method of choice for the detection of local recurrences.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physiological determinants of the variation in left ventricular mass from early adolescence to late adulthood in healthy subjects

BACKGROUND: The physiological determinants of left ventricular mass (LVM) measured by cardiac magnetic resonance (CMR) imaging are not well defined as prior investigators have studied either adults or adolescents in isolation or have not strictly excluded hypertension or accounted for the effects of exercise habits, haemodynamic, demographic, or body shape characteristics. METHODS: A total of 102 healthy volunteers (12-81 years, 53 males) underwent CMR. All parameters [unstandardized and adjusted for body surface area (BSA)] were analysed according to gender and by adolescence versus adulthood (adolescents <20 years, adults > or = 20 years). The influence of haemodynamic factors, exercise, and demographic factors on LVM were determined with multivariate linear regression. Results: LVM rose during adolescence and declined in adulthood. LVM and LVMBSA were higher in males both in adults (LVM: 188 +/- 22 g versus 139 +/- 21 g, P < 0.001; LVMBSA: 94 +/- 11 g m(-2) versus 80 +/- 11 g m(-2), P < 0.001) and in adolescents when adjusted for BSA (LVM: 128 +/- 29 g versus 107 +/- 20 g, P = 0.063; LVMBSA: 82 +/- 8 g m(-2) versus 71 +/- 10 g m(-2), P = 0.025). In adults, systolic blood pressure (SBP) and self-reported physical activity increased while meridional and circumferential wall stress were constant with age. Multivariate regression analysis revealed age, gender, and BSA as the major determinants of LVM (global R2 = 0.69). CONCLUSIONS: Normal LVM shows variation over a broad age range in both genders with a rise in adolescence and subsequent decline with increasing age in adulthood despite an increase in SBP and physical activity. BSA, age, and gender were found to be major contributors to the variation in LVM in healthy adults, while haemodynamic factors, exercise, and wall stress were not.     

Reference left atrial dimensions and volumes by steady state free precession cardiovascular magnetic resonance

Background

Left atrial (LA) size is related to cardiovascular morbidity and mortality. Cardiovascular magnetic resonance (CMR) provides high quality images of the left atrium with high temporal resolution steady state free precession (SSFP) cine sequences. We used SSFP cines to define normal ranges for LA volumes and dimensions relative to gender, age and body surface area (BSA), and examine the relative value of 2D atrial imaging techniques in patients.For definition of normal ranges of LA volume we studied 120 healthy subjects after careful exclusion of cardiovascular abnormality (60 men, 60 women; 20 subjects per age decile from 20 to 80 years). Data were generated from 3-dimensional modeling, including tracking of the atrioventricular ring motion and time-volume curves analysis. For definition of the best 2D images-derived predictors of LA enlargement, we studied 120 patients (60 men, 60 women; age range 20 to 80 years) with a clinical indication for CMR.

Results

In the healthy subjects, age was associated with LA 4-chamber transverse and 3-chamber anteroposterior diameters, but not with LA volume. Gender was an independent predictor of most absolute LA dimensions and volume, but following normalization to BSA, some associations became non-significant. CMR normal ranges were modeled and are tabled for clinical use with normalization, where appropriate, for BSA and gender and display of parameter variation with age. The best 2D predictors of LA volume were the 2-chamber area and 3-chamber area (both r = 0.90, p < 0.001).

Conclusions

These CMR data show that LA dimensions and volume in healthy, individuals vary significantly by BSA, with lesser effects of age and gender.     

Background, rationale, and design of a clinical trial to assess the effects of platelet dose on bleeding risk in thrombocytopenic patients

Outlined is the background and rationale for the initiation of a randomized prospective platelet transfusion trial to evaluate the effects of platelet dose on hemostasis and platelet utilization rates. This clinical trial is being performed by the newly established Transfusion Medicine/Hemostasis Clinical Trial Network supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health. The trial will randomize 1,350 patients into three platelet transfusion arms based on body surface area (BSA). The lower dose will be 1.1 x 10(11) platelets/m(2), the medium dose will be 2.2 x 10(11) platelets/m(2), and the higher dose will be 4.4 x 10(11) platelets/m(2). The primary outcome measure will be the incidence of Grade 2 bleeding; i.e., gross hemorrhage without the need for red cell transfusion. Major secondary outcome measures will be the total number of platelets transfused, the total number of platelet transfusion events, the highest grade of bleeding, and bleeding severity. It is expected that this clinical trial will change platelet transfusion practice by identifying whether low-dose platelet transfusion therapy provides adequate hemostasis and what is the most cost-effective strategy for providing platelet transfusions.     

The reliability and validity of the physiological cost index in healthy subjects while walking on 2 different tracks

OBJECTIVE: To investigate the reliability and validity of the Physiological Cost Index (PCI) scores, as a measure of energy expenditure, when healthy subjects walk on 2 different tracks (20-m and 12-m figure eight tracks). DESIGN: Intra- and interrater reliability and construct validity. SETTING: Physiotherapy division of a university in London, UK. PARTICIPANTS: Forty healthy subjects (15 men, 25 women; mean age +/- standard deviation, 34.5+/-12.6 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Heart rate (in beats/min) and speed (in m/min) were used to calculate the PCI (in beats/m). Rate of oxygen consumption (VO2, in mL x kg(-1) x min(-1)) and oxygen cost (EO2, in mL x kg(-1) x m(-1)) were used as criterion estimates of energy cost EO2. Pearson correlation coefficients between the PCI, components of the PCI, EO2, and VO2 were used to quantify validity. Intrarater reliability was assessed in all participants and interrater reliability was assessed on a subset of 13 subjects using intraclass correlation coefficients and Bland-Altman plots. RESULTS: Intrarater (r=.73, r=.79) and interrater (r=.62, r=.66) reliability were acceptable between PCI scores from 20-m and 12-m tracks, respectively. Correlations between VO2 and EO2 with PCI were weak. PCI scores from the 20-m track were significantly lower than those on the 12-m track (P=.002). Subjects walked significantly faster on the 20-m track (P<.001). Results suggest a large difference in PCI scores would be necessary to indicate a "true" alteration in performance (52% for 20-m track, 43.4% for the 12-m track). CONCLUSIONS: The PCI is reliable but not valid as a measure of the energy cost of walking in healthy subjects, on either track. The 20-m track is recommended for clinical use because it enables subjects to walk at a faster pace.     

替吉奥胶囊联合奥沙利铂治疗晚期结直肠癌的临床观察

目的观察替吉奥胶囊联合奥沙利铂治疗晚期结直肠癌的近期疗效和毒性反应。方法 2011年5月-12月,将30例晚期结直肠癌患者根据体表面积来确定初始剂量,体表面积<1.25 m2者,替吉奥胶囊40 mg/次,2次/d;体表面积1.25～1.50 m2者,替吉奥胶囊50 mg/次,2次/d;体表面积>1.50 m2者,替吉奥胶囊60 mg/次,2次/d。早饭后和晚饭后分别口服1次,第1～4天服用奥沙利铂注射液130 mg/m2,静脉滴注,第1、21天重复,此为1个月周期。连用2周期后,按美国国立癌症研究所拟定的药物不良反应的分级评价标准3.0版本评价不良反应,按实体瘤治疗疗效评价标准评价疗效。结果 30例患者中,完全缓解1例(3.3%),部分缓解7例(23.3%),稳定12例(40%),进展10例(33.3%),疾病控制率为66.6%。不良反应主要是血液学毒性、胃肠道反应、皮肤色素沉着及外周神经毒性;1例Ⅳ度骨髓抑制,3例3度贫血,2例3度腹泻,2例3度皮肤色素沉着,2例3度恶心、呕吐,其余且均在Ⅰ～Ⅱ度骨髓抑制。结论替吉奥胶囊联合奥沙利铂方案治疗晚期结直肠癌可获得较高的疾病控制率,不良反应可控。     

Effect of dopamine-induced changes in splanchnic blood flow on MEGX production from lidocaine in septic and cardiac surgery patients

The production of monoethylglycine xylidide (MEGX) from lidocaine is thought to be dependent on hepatic blood flow. We assessed the relationship between hepatosplanchnic blood flow, lidocaine uptake, and the production of MEGX from lidocaine in seven patients after cardiac surgery and in nine septic patients. Systemic (pulmonary artery catheter) and splanchnic (hepatic vein catheter and dye dilution) hemodynamics and arterial and hepatic venous lidocaine and MEGX concentrations were measured after a lidocaine bolus injection (1 mg/kg) before and 90 min after increasing cardiac output by at least 25% with dopamine. Dopamine infusion [in cardiac surgery patients 4.2 (1.4-8.5) microg x kg(-1) x min(-1) (median, range) and in septic patients 4.0 (2.1-9.0) microg x kg(-1) x min(-1)] increased splanchnic blood flow in cardiac surgery patients from 0.65 (0.12) L x min(-1) x m(-2) to 0.84 (0.14) L x min(-1) x m(-2) mean (standard deviation) P = 0.018) and in septic patients from 0.91 (0.32) L x min(-1) x m(-2) to 1.12 (0.40) L x min(-1) x m(-2) (P = 0.038). Splanchnic MEGX production for the 30 min after lidocaine injection was higher in cardiac surgery patients than in septic patients both at baseline [4130 (1100) microg x m(-2) vs. 930 (420) microg x m(-2) (P < 0.005)] and afterdopamine infusion [4480 (1000) microg x m(-2) vs. 1090 (620) microg x m(-2) (P = 0.005)]. We found no correlation between changes in MEGX production and changes in splanchnic blood flow. Patients with sepsis have severe impairment of cytochrome P450-dependent liver function, which is not influenced by acute changes in hepatosplanchnic blood flow. MEGX production cannot be used as an estimate of changes in splanchnic blood flow.     

Physiological determinants of the variation in left ventricular mass from early adolescence to late adulthood in healthy subjects

BACKGROUND: The physiological determinants of left ventricular mass (LVM) measured by cardiac magnetic resonance (CMR) imaging are not well defined as prior investigators have studied either adults or adolescents in isolation or have not strictly excluded hypertension or accounted for the effects of exercise habits, haemodynamic, demographic, or body shape characteristics. METHODS: Ninety-seven healthy volunteers (11-81 years, 51 males) underwent CMR. All parameters [unstandardized and adjusted for body surface area (BSA)] were analysed according to gender and by adolescence versus adulthood (adolescents<20 years, adults>or=20 years). The influence of haemodynamic factors, exercise and demographic factors on LVM were determined with multivariate linear regression. RESULTS: Left ventricular mass rose during adolescence and declined in adulthood. LVM and LVMBSA were higher in males both in adults (LVM: 188+/-22 versus 140+/-21 g, P<0.001; LVMBSA: 94+/-11 versus 80+/-11 g m(-2), P<0.001) and in adolescents when adjusted for BSA (LVM: 128+/-29 versus 107+/-20 g, P=0.063; LVMBSA: 82+/-8 versus 71+/-10 g m(-2), P=0.025). In adults, systolic blood pressure (SBP) and self-reported physical activity increased while meridional and circumferential wall stress were constant with age. Multivariate regression analysis revealed age, gender and BSA as the major determinants of LVM (global R2=0.68). CONCLUSIONS: Normal LVM shows variation over a broad age range in both genders with a rise in adolescence and subsequent decline with increasing age in adulthood despite an increase in SBP and physical activity. BSA, age and gender were found to be major contributors to the variation in LVM in healthy adults, while haemodynamic factors, exercise and wall stress were not.     

Monitoring kidney function in type 2 diabetic patients with incipient and overt diabetic nephropathy

OBJECTIVE: The purpose of this study was to assess agreement between glomerular filtration rate (GFR) and the decline in GFR estimated with the Modification of Diet in Renal Disease (MDRD) Study Group equation or the Cockcroft-Gault formula and measured by the plasma clearance of 51Cr-EDTA. RESEARCH DESIGN AND METHODS: We followed a cohort of 156 microalbuminuric type 2 diabetic patients for 8 years with four measurements of GFR and another cohort of 227 type 2 diabetic patients with overt diabetic nephropathy for 6.5 (range 3-17) years with seven (3-22) measurements of GFR. RESULTS: For patients with microalbuminuria, mean +/- SD baseline GFR was 117 +/- 24 measured, 92 +/- 20 estimated (MDRD equation), or 103 +/- 24 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001); 95% limits of agreement were -66.1 to 20.3 (MDRD equation) and -58.7 to 30.7 (Cockcroft-Gault formula). The rate of decline in GFR was 4.1 +/- 4.2 measured, 2.9 +/- 2.8 estimated (MDRD equation), or 3.4 +/- 3.2 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001). For patients with overt nephropathy, baseline GFR was 84 +/- 30 measured, 73 +/- 24 estimated (MDRD equation), or 81 +/- 28 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001) with 95% limits of agreement -47 to 25 (MDRD equation) and -39 to 33 (Cockcroft-Gault formula). The rate of decline in GFR was 5.2 +/- 4.1 measured, 4.2 +/- 3.8 estimated (MDRD equation), and 4.6 +/- 4.1 ml x min(-1) per 1.73 m2 estimated (Cockcroft-Gault formula) (both P < 0.001). CONCLUSIONS: Particularly in microalbuminuric (hyperfiltering) patients, GFR is significantly underestimated with wide limits of agreement by the MDRD equation as well as by the Cockcroft-Gault formula. The rate of decline in GFR is also significantly underestimated with both equations. This makes GFR estimations based upon these equations unacceptable for monitoring kidney function in type 2 diabetic patients with incipient and overt diabetic nephropathy.     

Follow-up study of peritoneal fluid kinetics in infants and children on peritoneal dialysis.

OBJECTIVES: To study longitudinal changes in transcapillary ultrafiltration (TCUF) and marker clearance (MC), as a reflection of lymphatic absorption, in children on peritoneal dialysis (PD). To present data on fluid kinetics in infants younger than 2.5 years, using an intraperitoneal volume of 1200 mL/m2 body surface area (BSA). DESIGN: The study involved a 4-hour dwell of 1200 mL/m2 BSA of dialysis fluid containing 3.86% glucose with Dextran 70 as volume marker. Cumulative TCUF and cumulative MC were measured. SETTING: A tertiary-care university hospital. PATIENTS: A follow-up period of 33 months of serial (1 - 4) peritoneal equilibration tests (PETs) was studied in 20 children with a median age of 6.4 years (range 2.1 - 15.4 years). Fluid kinetics in 5 additional infants with a median age of 1.4 years (range 0.5 - 2.5 years) was measured. RESULTS: Cumulative TCUF was 1041 mL/1.73 m2 at 1 - 3 months after start of PD, 1026 mL/1.73 m2 at 7 - 9 months, 1021 mL/1.73 m2 at 11 - 13 months, and 756 mL/1.73 m2 at 26 - 33 months (NS). Cumulative MC was 235 mL/1.73 m2 at 1 - 3 months after start of PD, 311 mL/1.73 m2 at 7 - 9 months, 395 mL/1.73 m2 at 11 - 13 months, and 509 mL/1.73 m2 at 26 - 33 months (NS). In infants, cumulative TCUF was 755 +/- 237 mL/1.73 m2; cumulative MC was 400 +/- 214 mL/1.73 m2. CONCLUSIONS: Transcapillary ultrafiltration and marker clearance do not change in children > 2.5 years during the period studied. Fluid kinetics does not differ between infants < 2.5 years and older children when intraperitoneal volumes of 1200 mL/m2 BSA are used.     

Electrocardiographic diagnosis of hypertrophy of the left ventricular myocardium in patients with arterial hypertension and overweight

AIM: To study efficacy of different ECG criteria of hypertrophy of left ventricular myocardium (LVH) in hypertensive patients with reference to overweight and obesity. MATERIAL AND METHODS: The authors analyse data on 100 patients (42 males and 58 females) aged 19-79 with diagnosis of arterial hypertension stage I-II. ECG was conducted in 12 leads. LVH by ECG was determined according to the following criteria: Sokolov-Lyon (S-L): Sv1+Rv5(v6) > 35 mm; Cornell voltage (Crn V): R avL +Sv3 > 28 mm (> 20 mm for females; Cornell product (Crn P): (RavL+Sv3)xQRSduration > 2440 mm x ms (for females RavL+Sv3 amplitudes + 0.6 mm). To verify L VH by echoCG, the authors used threshold values of left ventricular myocardium mass index (LVMMI) 125 g/m(2) for males and 110 g/m(2) for females. LVMMI was calculated by two methods: LVMM to body surface area (BSA) 2) LVMM to BSA of an ideal figure of a relevant height. Depending on the BMI all the patients were divided into 3 groups: with normal weight (BMI under 25 kg/m2), with overweight (BMI between 25 and 30 kg/m(2)), with obesity (BMI over 30 kg/m(2)). RESULTS: Sensitivity of the criterion Crn-P was the highest. The S-L criterion had the least sensitivity (under 10%) in groups with overweight by more than 25 kg/m(2). In these groups sensitivity of all ECG criteria of L VH depends on some factors: on indexation of LVH by body size, gender and overweight. S-L criterion sensitivity is higher in subgroups of males irrespective of overweight and obesity. CONCLUSION: Informative value of LVH ECG criteria depends on the method of LVMM indexation by body size, overweight and gender of the patients.     

Enhanced endothelin(A) receptor-mediated calcium mobilization and contraction in organ cultured porcine coronary arteries

Arterial injury models for coronary artery disease have demonstrated an enhanced expression and function of either the endothelin(A) or endothelin(B) (ET(A) or ET(B)) receptor subtype. We hypothesized that organ culture would enhance the physiological function of ET receptors in the porcine right coronary artery. Arteries were either cold stored (4 degrees C) or organ cultured (37 degrees C) for 4 days. After 4 days, the artery was either 1) sectioned into rings to measure the ET-1-induced isometric tension response (3 x 10(-10)-3 x 10(-7) M), or 2) enzymatically dispersed and the isolated smooth muscle cells imaged using fura-2 to measure the myoplasmic calcium (Ca(m)) response to 3 x 10(-8) M ET-1 ( approximately EC(50)). Isometric tension and Ca(m) to ET-1 were measured in the absence and presence of bosentan (nonselective ET(A) or ET(B) receptor antagonist), BQ788 (ET(B)-selective antagonist), and BQ123 (ET(A)-selective antagonist). Compared with cold storage, organ culture induced a 2-fold increase in tension development (3 x 10(-7) M ET-1) and Ca(m) (3 x 10(-8) M ET-1), which was inhibited with bosentan, thus confirming the enhanced responses to ET-1 were due to ET receptor activation. BQ123 also inhibited the enhanced contraction and Ca(m) responses to ET-1. In contrast, BQ788 failed to inhibit tension development and Ca(m) responses to ET-1 in organ culture and cold storage. Sarafotoxin 6C (ET(B) agonist) failed to elicit an increased Ca(m) response in organ culture compared with cold storage. Our results indicate the increased tension development and Ca(m) responses to ET-1 in organ culture are attributable to ET(A) receptors, and not ET(B) receptors.     

Effect of body surface area calculations on body fat estimates in non-obese and obese subjects

The purpose of the present study was to compare body surface area (BSA) estimates using two equations (Dubois and Dubois versus Livingston) and their respective effects on per cent body fat (%BF) obtained with two molecular approaches of body composition analysis, two-compartment (2C) and five-compartment (5C) models. Body composition data using the 2C model were studied in healthy adults, 432 women (body mass index (BMI): 28.3 +/- 4.4 kg m(-2)) and 147 men (BMI: 26.8 +/- 3.9 kg m(-2)), while another sample of 126 women (BMI: 30.4 +/- 3.7 kg m(-2)) was evaluated using the 5C model. Measures of body volume (BV) assessed by air displacement plethysmography, bone mineral content by dual energy x-ray absorptiometry (DXA) and total-body water by deuterium dilution were used to estimate %BF with the 5C model. Comparison of means and linear regression analysis was performed. Using BSA(Dubois), either in 2C and 5C models, BV and %BF estimates were significantly underestimated compared to results obtained using BSA(Livingston) (p < 0.05). BMI was strongly associated with %BF differences using BSA(Dubois) and BSA(Livingston) in both 2C (men: r = 0.90; women: r = 0.88) and 5C models (r = 0.88). Though %BF(Dubois) and %BF(Livingston) were strongly associated (r(2) = 1.000), some variability was observed on %BF differences using BSA(Dubois) and BSA(Livingston). These findings suggest that BSA calculation is critical in BF estimation, supporting the use of a more accurate equation for non-obese and obese subjects.