Leigh C. Ward

Quantification of lean bodyweight

AbstractBackground: Lean bodyweight (LBW) has been recommended for scaling drug doses. However, the current methods for predicting LBW are inconsistent at extremes of size and could be misleading with respect to interpreting weight-based regimens. Objective: The objective of the present study was to develop a semi-mechanistic model to predict fat-free mass (FFM) from subject characteristics in a population that includes extremes of size. FFM is considered to closely approximate LBW. There are several reference methods for assessing FFM, whereas there are no reference standards for LBW. Patients and methods: A total of 373 patients (168 male, 205 female) were included in the study. These data arose from two populations. Population A (index dataset) contained anthropometric characteristics, FFM estimated by dual-energy x-ray absorptiometry (DXA — a reference method) and bioelectrical impedance analysis (BIA) data. Population B (test dataset) contained the same anthropometric measures and FFM data as population A, but excluded BIA data. The patients in population A had a wide range of age (18–82 years), bodyweight (40.7–216.5kg) and BMI values (17.1–69.9 kg/m2). Patients in population B had BMI values of 18.7–38.4 kg/m2. A two-stage semi-mechanistic model to predict FFM was developed from the demographics from population A. For stage 1 a model was developed to predict impedance and for stage 2 a model that incorporated predicted impedance was used to predict FFM. These two models were combined to provide an overall model to predict FFM from patient characteristics. The developed model for FFM was externally evaluated by predicting into population B. Results: The semi-mechanistic model to predict impedance incorporated sex, height and bodyweight. The developed model provides a good predictor of impedance for both males and females (r2 = 0.78, mean error [ME] = 2.30 × 10−3, root mean square error [RMSE] = 51.56 [approximately 10% of mean]). The final model for FFM incorporated sex, height and bodyweight. The developed model for FFM provided good predictive performance for both males and females (r2 = 0.93, ME = −0.77, RMSE = 3.33 [approximately 6% of mean]). In addition, the model accurately predicted the FFM of subjects in population B (r2 = 0.85, ME = −0.04, RMSE = 4.39 [approximately 7% of mean]). Conclusions: A semi-mechanistic model has been developed to predict FFM (and therefore LBW) from easily accessible patient characteristics. This model has been prospectively evaluated and shown to have good predictive performance.

High-carbohydrate high-fat diet–induced metabolic syndrome and cardiovascular remodeling in rats.

The prevalence of metabolic syndrome including central obesity, insulin resistance, impaired glucose tolerance, hypertension, and dyslipidemia is increasing. Development of adequate therapy for metabolic syndrome requires an animal model that mimics the human disease state. Therefore, we have characterized the metabolic, cardiovascular, hepatic, renal, and pancreatic changes in male Wistar rats (8-9 weeks old) fed on a high-carbohydrate, high-fat diet including condensed milk (39.5%), beef tallow (20%), and fructose (17.5%) together with 25% fructose in drinking water; control rats were fed a cornstarch diet. During 16 weeks on this diet, rats showed progressive increases in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia, hyperinsulinemia, and increased plasma leptin and malondialdehyde concentrations. Cardiovascular signs included increased systolic blood pressure and endothelial dysfunction together with inflammation, fibrosis, hypertrophy, increased stiffness, and delayed repolarization in the left ventricle of the heart. The liver showed increased wet weight, fat deposition, inflammation, and fibrosis with increased plasma activity of liver enzymes. The kidneys showed inflammation and fibrosis, whereas the pancreas showed increased islet size. In comparison with other models of diabetes and obesity, this diet-induced model more closely mimics the changes observed in human metabolic syndrome.

Improved prediction of extracellular and total body water using impedance loci generated by multiple frequency bioelectrical impedance analysis

Bioelectrical impedance analysis (BIA) using a frequency of 50 kHz is an established method of predicting total body water (TBW). However, very little research has been performed to determine whether 50 kHz is the optimum frequency for the prediction of TBW from impedance measurements. This paper analyses a mathematical expression describing the equivalent electrical circuit for biological tissue, and derives a graphical representation of the resistive and reactive components. The nature of the resulting impedance locus was used in the analysis of measured whole-body impedance of 42 rats over a range of frequencies to determine the impedance at the characteristic frequency, Zc, and also the impedance at zero frequency, R0. The standard error associated with the prediction of TBW (determined by isotope dilution) using Zc was 5.9% compared with a standard error of prediction of 10.1% using the established BIA method at 50 kHz on the same data. Predictions of extracellular water (ECW) using the impedance at zero frequency, R0, yielded a standard error of 3.2% compared with standard errors of 4.8% and 4.2% using single frequency BIA measurements at 5 kHz and 1 kHz, respectively. These results demonstrate a significant (P < 0.01) improvement in the prediction of TBW and ECW using multiple frequency bioelectrical impedance analysis (MFBIA).

Nutritional rehabilitation in cystic fibrosis: Controlled studies of effects on nutritional growth retardation, body protein turnover, and course of pulmonary disease

The effects of a sustained increase in energy and protein intake on weight gain, growth, body protein metabolism, and the course of pulmonary disease were studied in 10 undernourished patients with cystic fibrosis unable to maintain nutrition and growth by the oral route and with declining nutritional and pulmonary status in the year prior to study. A 1-year course of nutrient supplementation using a semielemental high-nitrogen formula was delivered by nocturnal intragastric feeding or as an orally administered supplement; progress was compared with that of 14 height-, sex- and FEV1-matched patients with cystic fibrosis receiving conventional therapy. Supplementation resulted in a catch-up weight gain and sustained improvement in linear growth, with fewer pulmonary infections per year than during the initial observation period. Better weight gain and linear growth than in the comparison group were observed, as well as a significant reversal of the trend for deteriorating lung function. Compared with data from healthy children, 15N-glycine kinetics demonstrated increased protein breakdown and negligible net protein deposition in the treatment group prior to supplementation. After supplementation, synthesis in excess of breakdown, with net protein accretion, occurred by 1 month of supplementation. By 6 to 12 months a significant reduction in the previously high rate of mean synthesis and breakdown was observed, with maintenance of net anabolism. These dynamic changes in whole-body protein turnover reflect a long-term improvement in energy and protein intake, which can favorably affect nutrition, growth, and the course of pulmonary disease in problem cases of cystic fibrosis.

Assessment of breast cancer-related arm lymphedema--comparison of physical measurement methods and self-report.

ABSTRACT Purpose To determine the relationship between physical methods of measuring lymphedema and self-reported swelling, their reliability, and standard error of measurement. Method: Lymphedema in each arm of women with (n = 33) and without (n = 18) unilateral arm lymphedema, secondary to breast cancer was measured by self-report, bioimpedance spectroscopy (BIS), perometer, and the truncated cone method. Results: The physical measurement tools were highly reliable (ICC(2,1): 0.94 to 1.00) with high concordance (rc: 0.89 to 0.99). Selfreport correlatedmoderately with physical measurements (r = 0.65 to 0.71) and was moderately reliable (ICC(2,1): 0.70). Conclusions: Lymphedema assessment methods are concordant and reliable but not interchangeable.

Bioelectrical impedance for monitoring the efficacy of lymphoedema treatment programmes

The treatment of lymphoedema includes a combination of massage, compression bandaging, and exercise. To date the most common technique of assessing the efficacy of treatment has involved estimating the total limb volume from circumferential measurements at fixed intervals along the limb. This study investigated the application of multiple frequency bioelectrical impedance analysis, MFBIA, to monitor the volume of lymphoedema in the upper limb of patients who developed this disorder following surgery for cancer of the breast. Daily measurements of both circumference and impedance of both the affected and unaffected limbs were recorded for 20 patients throughout their 4 week treatment programmes. Twenty control subjects were also monitored daily over a similar 4 week period. Prior to the commencement of treatment the bioimpedance technique detected a significant (P < 0.01) asymmetry between the two limbs of the control subjects, associated with handedness (P < 0.001). Circumferential estimates of limb volumes in the control group detected no asymmetry. Impedance measures of extracellular fluid showed all of the patients to lie outside the 95% confidence interval determined from the data of the control group. The trends of the impedance measures and the circumferential estimates of volume throughout the 4 week program were found to be significantly different (P < 0.05); MFBIA exhibiting a greater sensitivity in the detection of lymphoedema. The results demonstrate that MFBIA is significantly more sensitive than circumferential measurement both in the early diagnosis of lymphoedema and in monitoring change.

Optimizing electrode sites for segmental bioimpedance measurements

Recent advances in the application of bioelectrical impedance analysis (BIA) have indicated that a more accurate approach to the estimation of total body water is to consider the impedance of the various body segments rather than simply that of the whole body. The segmental approach necessitates defining and locating the physical demarcation between both the trunk and leg and the trunk and arm. Despite the use of anatomical markers, these points of demarcation are difficult to locate with precision between subjects. There are also technical problems associated with the regional dispersion of the current distribution from one segment (cylinder) to another of different cross-sectional area. The concept of equipotentials in line with the proximal aspects of the upper (and lower) limbs along the contralateral limbs was investigated and, in particular, the utility of this concept in the measurement of segmental bioimpedance. The variation of measured segmental impedance using electrode sites along these equipotentials was less than 2.0% for all of the commonly used impedance parameters. This variation is approximately equal to that expected from biological variation over the measurement time. It is recommended that the electrode sites, for the measurement of segmental bioelectrical impedance in humans, described herein are adopted in accordance with the proposals of the NIH Technology Assessment Conference Statement.

Bioimpedance spectrometry in the determination of body water compartments: Accuracy and clinical significance

Bioelectrical impedance analysis (BIA) offers the potential for a simple, portable and relatively inexpensive technique for the in vivo measurement of total body water (TBW). The potential of BIA as a technique of body composition analysis is even greater when one considers that body water can be used as a surrogate measure of lean body mass. However, BIA has not found universal acceptance even with the introduction of multi-frequency BIA (MFBIA) which, potentially, may improve the predictive accuracy of the measurement. There are a number of reasons for this lack of acceptance, although perhaps the major reason is that no single algorithm has been developed which can be applied to all subject groups. This may be due, in part, to the commonly used wrist-to-ankle protocol which is not indicated by the basic theory of bioimpedance, where the body is considered as five interconnecting cylinders. Several workers have suggested the use of segmental BIA measurements to provide a protocol more in keeping with basic theory. However, there are other difficulties associated with the application of BIA, such as effects of hydration and ion status, posture and fluid distribution. A further putative advantage of MFBIA is the independent assessment not only of TBW but also of the extracellular fluid volume (ECW), hence heralding the possibility of being able to assess the fluid distribution between these compartments. Results of studies in this area have been, to date, mixed. Whereas strong relationships of impedance values at low frequencies with ECW, and at high frequencies with TBW, have been reported, changes in impedance are not always well correlated with changes in the size of the fluid compartments (assessed by alternative and more direct means) in pathological conditions. Furthermore, the theoretical advantages of Cole-Cole modelling over selected frequency prediction have not always been apparent. This review will consider the principles, methodology and applications of BIA. The principles and methodology will be considered in relation to the basic theory of BIA and difficulties experienced in its application. The relative merits of single and multiple frequency BIA will be addressed, with particular attention to the latters role in the assessment of compartmental fluid volumes.

Multi-frequency bioelectrical impedance augments the diagnosis and management of lymphoedema in post-mastectomy patients

Abstract. The value of multiple frequency bioelectric impedence analysis (MFBIA) in the monitoring and management of post‐mastectomy lymphoedema of the arm was evaluated in 15 patients and controls. The technique was found to produce quantitative agreement with a clinical diagnosis of lymphoedema and with the currently‐used measure (limb volume calculated from circumferential measurements) of limb size. The significance of this finding lies in MFBIA being diagnostically informative: it indicates when an observed change in limb volume is directly, albeit theoretically, attributable to accumulation of extracellular fluid. MFBIA potentially offers the means for earlier definitive diagnosis and more‐accurate monitoring of extracellular fluid changes during and after treatment.

Effects of ALA, EPA and DHA in high-carbohydrate, high-fat diet-induced metabolic syndrome in rats

We compared the cardiovascular, hepatic and metabolic responses to individual dietary n-3 fatty acids (α-linolenic acid, ALA; eicosapentaenoic acid, EPA; and docosahexaenoic acid, DHA) in a high-carbohydrate, high-fat diet-induced model of metabolic syndrome in rats. Additionally, we measured fatty acid composition of plasma, adipose tissue, liver, heart and skeletal muscle in these rats. The same dosages of ALA and EPA/DHA produced different physiological responses to decrease the risk factors for metabolic syndrome. ALA did not reduce total body fat but induced lipid redistribution away from the abdominal area and favorably improved glucose tolerance, insulin sensitivity, dyslipidemia, hypertension and left ventricular dimensions, contractility, volumes and stiffness. EPA and DHA increased sympathetic activation, reduced the abdominal adiposity and total body fat and attenuated insulin sensitivity, dyslipidemia, hypertension and left ventricular stiffness but not glucose tolerance. However, ALA, EPA and DHA all reduced inflammation in both the heart and the liver, cardiac fibrosis and hepatic steatosis. These effects were associated with complete suppression of stearoyl-CoA desaturase 1 activity. Since the physiological responses to EPA and DHA were similar, it is likely that the effects are mediated by DHA with EPA serving as a precursor. Also, ALA supplementation increased DHA concentrations but induced different physiological responses to EPA and DHA. This result strongly suggests that ALA has independent effects in metabolic syndrome, not relying on its metabolism to DHA.