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Biomedical subjects

L C Ward

Publications and source records attributed to L C Ward.

At least 19 recordsLinked to original sources

Bone density changes in Paget's disease 2 years after iv pamidronate: profound, sustained increases in pagetic bone with severity-related loss in forearm nonpagetic cortical bone.

Bone mineral density (BMD) was measured at three sites (forearm, spine, and hip) using dual X-ray and single-photon absorptiometry in 68 patients with Paget's disease before and after treatment with iv pamidronate. Patients were treated according to the severity of their disease; the mild category (Group I, hydroxyproline excretion (Hyp(E)) <5.0 micromol/L GF) received 120 mg, the moderate category (Group II, Hyp(E) 5.0-9.99 micromol/GF) 180 mg, and the severe category (Group III, > or = 10.0 micromol/GF) 240 mg. Group I was followed for 1 year, and both Groups II and III for 2 years. At the lumbar spine in pagetic bone there were no differences between groups in early responses, with a profound increase 6 months after treatment 20.5 +/- 2.0% above baseline values to 1.403 +/- 0.063 g/cm(2) (mean +/- SEM)(P < 0.001). This increase in BMD was sustained to 2 years (1.355 +/- 0.078 g/cm(2), P < 0.001) and was 15.0 +/- 2.2% above baseline values. The pagetic total hip BMD increased after treatment in all groups, with a mean rise of 10.4 +/- 1.4% at 1 year to 1.505 +/- 0.083 g/cm(2) (P < 0.01). At the pagetic femoral neck the response was similar, with a peak significant rise at 1 year of 10.7 +/- 1.7% to 1.403 +/- 0.097 g/cm(2) (P < 0.01). In nonpagetic spinal bone there were no differences between the group responses, with a combined mean increase of 4.3 +/- 0.7% at 1 year to 0.999 +/- 0.027 g/cm(2) (P < 0.01). In both Groups II and III the increase in BMD was significantly higher than baseline values at 1 and 2 years (P < 0.01). In the nonpagetic total hip BMD remained unchanged over the 2-year period and likewise, there were no significant changes from baseline at the nonpagetic femoral neck site. In the nonpagetic forearm we found a significant loss in BMD at the ultradistal (mainly trabecular), midregion (80% cortical), and proximal shaft (95% cortical) sites in Group III, persisting to 2 years at the latter two sites. The increase in bone density in pagetic bone, persisting at least 2 years, provides a new modality of assessment of the response of pagetic bone to treatment and suggests a mechanism for the reduction in fracture risk in such bone after effective bisphosphonate treatment. Severity-dependent nonpagetic forearm bone loss, persisting to 2 years at cortical sites, suggests a potential drug-induced fracture risk at the forearm and possibly elsewhere in the absence of appropriate preventive cotreatment.

Aged↗

Estimation of body water compartments in cirrhosis by multiple-frequency bioelectrical-impedance analysis.

Estimation of total body water by measuring bioelectrical impedance at a fixed frequency of 50 kHz is useful in assessing body composition in healthy populations. However, in cirrhosis, the distribution of total body water between the extracellular and intracellular compartments is of greater clinical importance. We report an evaluation of a new multiple-frequency bioelectrical-impedance analysis technique (MFBIA) that may quantify the distribution of total body water in cirrhosis. In 21 cirrhotic patients and 21 healthy control subjects, impedance to the flow of current was measured at frequencies ranging from 4 to 1012 kHz. These measurements were used to estimate body water compartments and then compared with total body water and extracellular water determined by isotope methodology. In cirrhotic patients, extracellular water and total body water (as determined by isotope methods) were well predicted by MFBIA (r = 0.73 and 0.89, respectively). However, the 95% confidence intervals of the limits of agreement between MFBIA and the isotope methods were +/-14% and +/-9% for cirrhotics (extracellular water and total body water, respectively) and +/-9% and +/-9% for cirrhotics without ascites. The 95% confidence intervals estimated from the control group were +/-10% and +/-5% for extracellular water and total body water, respectively. Thus, despite strong correlations between MFBIA and isotope measurements, the relatively large limits of agreement with accepted techniques suggest that the MFBIA technique requires further refinement before it can be routinely used to determine the nutritional assessment of individual cirrhotic patients.

Ascites↗

Assessment of body composition by bioelectrical impedance analysis without the need for measurement of height.

Conventional whole-body single frequency bioelectrical impedance analysis (BIA) of body composition typically uses height as a surrogate measure of conductor length. A new method of BIA analysis for the prediction of body cell mass (BCM) and extracellular water (ECW, as % body weight) not using height has been introduced-the Soft Tissue Analyser (STA(TM), Akern Sri, Florence, Italy)-making it ideal for use in subjects where measurement of height is difficult or impossible. The performance of the new analytical method in predicting BCM and ECW in 139 normal control subjects was assessed by comparison with reference data obtained from a four-component (4-C) model of body composition and with predictions obtained from conventional BIA analysis. Both predicted BCM and ECW were strongly (r=0.82, SEE=6.3 kg and 0.89, SEE=1.3 kg respectively) correlated with the corresponding 4-C model measurements although differing significantly from the lines of identity (P<0.0001). Fat-free mass, calculated from STA estimates of BCM and ECW, was better predicted (r=0.91, SEE=5.6 kg). The significant differences in STA-group mean values for BCM and ECW and wide limits of agreement compared with the reference data indicate that the method cannot be used with confidence for prediction of these body compartments despite the obvious advantage of not requiring an accurate measurement of height.

Adult↗

Fluid shifts resulting from exercise in rats as detected by bioelectrical impedance.

PURPOSE: This study was designed to investigate the immediate effect of exercise intensity and duration on body fluid volumes in rats throughout a 3-wk exercise program. METHODS: Changes in the extracellular water (ECW) and total body water (TBW) volumes of rats were measured preexercise and postexercise using multiple frequency bioelectrical impedance analysis. Groups of rats were exercised at two intensities (6 m.min(-1) and 12 m.min(-1)) for two exercise times (60 min and 90 min) 5 d.wk(-1) during a 3-wk period. Changes in plasma electrolytes, glucose, and lactate resulting from the exercise were also measured on 3 d of each week. RESULTS: Each group of animals showed significant losses in ECW and TBW as a direct result of daily exercise. The magnitude of fluid loss was directly related to the intensity of the exercise, but not to exercise duration; although the magnitude of daily fluid loss at the higher intensity exercise (12 m.min(-1)) decreased as the study progressed, possibly indicating a training effect. CONCLUSION: At low-intensity exercise, there is a small but significant loss in both TBW and ECW fluids, and the magnitude of these losses does not change throughout a 3-wk exercise program. At moderate levels of exercise intensity, there is a greater loss of both TBW and ECW fluids. However, the magnitudes of these losses decrease significantly during the 3-wk exercise program, thus demonstrating a training effect.

Animals↗

Bisphosphonate therapy for Paget's disease in a patient with hypoparathyroidism: profound hypocalcemia, rapid response, and prolonged remission.

Bisphosphonate treatment for severe Paget's disease leads to hypocalcemia followed by a secondary hyperparathyroid response to restore normocalcemia. A case is presented of a 60-year-old woman with polyostotic Paget's disease and postsurgical hypoparathyroidism. In 1993 her Paget's disease--alkaline phosphatase (ALP), 1260 U/liter (35-135 U/liter), and fasting urinary hydroxyproline excretion, 13.7 micromol/liter GF (0.4-1.9 micromol/liter)--was treated with intravenous pamidronate. Symptomatic hypocalcemia followed the first 60-mg dose, requiring large doses of calcium supplementation and calcitriol. Pamidronate therapy to a total dose of 360 mg was followed by rapid and prolonged remission with indices of bone turnover in the normal range within 2 months and persisting for at least 19 months after treatment. In 1999 relapse of Paget's disease--ALP, 511 U/liter (35-135 U/liter), and fasting urinary deoxypyridinoline/creatinine 53.1 micromol/mol (5-27 micromol/mol)--was treated with alendronate, 10 mg daily. Symptomatic hypocalcemia occurred again, requiring increased calcium and calcitriol therapy. Indices of bone turnover were within the normal range 9 weeks after the start of therapy. These responses were significantly more rapid and sustained than those observed in euparathyroid subjects. This case suggests that the lack of parathyroid response may modify the response to bisphosphonates by: (a) increasing intrinsic uptake of bisphosphonate into the pagetic skeleton, allowing response to a smaller dose; (b) increasing duration and severity of hypocalcemia after bisphosphonate therapy; and (c) removing the hyperparathyroid drive to reactivation of pagetic osteoclasts, leading to a prolonged remission. These observations have implications for optimizing bisphosphonate therapy both in Paget's disease and in osteoporosis.

Alendronate↗

Early diagnosis of lymphedema using multiple frequency bioimpedance.

Multiple frequency bioelectrical impedance analysis (MFBIA) has previously been shown to provide accurate relative measures of lymphedema in the upper limb of patients (1). This paper reports the results of a three year prospective study to evaluate the efficacy of MFBIA to predict the early onset of lymphedema in patients following treatment for breast cancer. Bioelectrical impedance measurements and circumferential measurements of each upper limb were recorded in healthy control subjects (n = 60) to determine the normal range of the ratio (dominant/non-dominant) of extracellular and total limb volumes respectively. Patients undergoing surgery for the treatment of breast cancer were recruited as the study group; MFBIA and circumferential measurements were recorded pre-surgery, one month post-surgery and then at two month intervals for 24 months. One hundred and two patients were recruited into the study. Twenty patients developed lymphedema in the 24 months follow up period of this study. In each of these 20 cases MFBIA predicted the onset of the condition up to 10 months before the condition could be clinically diagnosed. Estimates of the sensitivity and specificity were both approximately 100%. At the time of detection by MFBIA, only one of the patients returned a positive test result from the total limb volumes determined from the circumferential measures. These results confirmed the suitability of the MFBIA technique as a reliable diagnostic procedure for the early detection of lymphedema.

Adult↗

Evaluation of a new bioelectrical impedance instrument for the prediction of body cell mass independently of height or weight.

The objective of the present study was to evaluate the performance of a new bioelectrical impedance instrument, the Soft Tissue Analyzer (STA), which predicts a subject's body composition. A cross-sectional population study in which the impedance of 205 healthy adult subjects was measured using the STA. Extracellular water (ECW) volume (as a percentage of total body water, TBW) and fat-free mass (FFM) were predicted by both the STA and a compartmental model, and compared according to correlation and limits of agreement analysis, with the equivalent data obtained by independent reference methods of measurement (TBW measured by D(2)O dilution, and FFM measured by dual-energy X-ray absorptiometry). There was a small (2.0 kg) but significant (P < 0.02) difference in mean FFM predicted by the STA, compared with the reference technique in the males, but not in the females (-0.4 kg) or in the combined group (0.8 kg). Both methods were highly correlated. Similarly, small but significant differences for predicted mean ECW volume were observed. The limits of agreement for FFM and ECW were -7.5-9.9 and -4.1-3.0 kg, respectively. Both FFM and ECW (as a percentage of TBW) are well predicted by the STA on a population basis, but the magnitude of the limits of agreement with reference methods may preclude its usefulness for predicting body composition in an individual. In addition, the theoretical basis of an impedance method that does not include a measure of conductor length requires further validation.

Absorptiometry, Photon↗

Identification and monitoring of disordered water balance: bioelectrical impedance analysis as an alternative to the target weight procedure.

Many psychiatric patients present with disorders of water balance manifested by polydipsia or polyuria. Multiple frequency bioelectrical impedance analysis (MFBIA) was investigated as a suitable method for the assessment of body water in such patients. Whole body bioelectrical impedance, total body water and extracellular water and serum sodium were measured in 10 chronic psychiatric inpatients with polydipsia. Fluid volumes predicted by MFBIA correlated significantly (P < 0.002) with those obtained by reference methods but the relatively high limits of agreement (2.2 L) suggest that the method is not yet sufficiently accurate for random screening purposes. However, owing to the simplicity and non-invasive nature of the technique, it warrants further investigation and development, particularly for routine patient monitoring.

Adult↗

Assessment of intracellular water by whole body bioelectrical impedance and total body potassium in HIV-positive patients.

OBJECTIVE: Bioelectrical impedance analysis (BIA) is widely used as bedside assessment of body composition. Body cell mass (BCM) and intracellular water (ICW) are clinically important body compartments. Estimates of ICW obtained from BIA by different calculation approaches were compared to a reference method in male HIV-infected patients. PATIENTS: Representative subsample of clinically stable HIV-infected outpatients, consisting of 42 men with a body mass index of 22.4 +/- 3.8 kg/m(2)(range, 13-l31 kg/m(2)). METHODS: Total body potassium was assessed in a whole body counter, and compared to 50 kHz monofrequency BIA and multifrequency bioelectrical impedance spectroscopy. Six different prediction equations for ICW from BIA data were applied. Methods were compared by the Bland-Altman method. RESULTS: BIA-derived ICW estimates explained 58% to 73% of the observed variance in ICW (TBK), but limits of confidence were wide (-16.6 to +18.2% for the best method). BIA overestimated low ICW (TBK) and underestimated high ICW (TBK) when normalized for weight or height. Mono- and multifrequency BIA were not different in precision but population-specific equations tended to narrower confidence limits. CONCLUSION: BIA is an unreliable method to estimate ICW in this population, in contrast to the better established estimation of total body water and extracellular water. Potassium depletion in severe malnutrition may contribute to this finding but a major part of the residual between methods remains unexplained.

Acquired Immunodeficiency Syndrome↗

Measurement of extracellular fluid volume in the neonate using multiple frequency bio-impedance analysis.

Bioelectrical impedance analysis may be useful for cot-side monitoring of fluid balance in the neonatal intensive care unit (NICU). However the presence of cardio-respiratory monitoring equipment, non-ideal electrode placement and inability to obtain accurate crown-heel measurements may interfere with the ability to obtain reliable impedance data in this setting. This study aimed to investigate the effects of these factors on impedance analysis and to develop a prediction equation for extracellular fluid volume in the neonate. The study found that cardio respiratory monitoring had no significant effect on multi-frequency impedance measurements. Placement of current delivering electrodes on the ventral rather than dorsal surfaces improved separation of current and voltage electrodes but did not alter impedance results. Contralateral measurements were not significantly different to ipsilateral measurements. In 24 infants, extracellular fluid volume was measured using corrected bromide space (CBS) and simultaneous impedance analysis was performed. There was good correlation between CBS and the impedance quotient FF2/Ro where F is foot length and R0 is resistance at zero frequency. The study concludes that despite many potential difficulties associated with impedance analysis in the NICU, reliable measurements of impedance can be obtained and further work to validate prediction equations for ECF is warranted.

Electric Impedance↗

Comparison of whole body and segmental bioimpedance methodologies for estimating total body water.

We compared the whole body (WB) and segmental bioelectrical impedance analysis (BIA) methodologies in a group of healthy adults (n = 25). It has been suggested that the segmental methodology may overcome the difficulty in generating a single algorithm to predict total body water (TBW) in all groups whether healthy or not. We measured TBW, using D2O dilution, and WB and segmental BIA parameters. Cole-Cole analysis was used to determine the impedance at the characteristic frequency (Zc). The correlation between TBW (by D2O dilution) and segmental BIA measures (multiple regression, r = 0.90, p < 0.001, SEE = 3.1 L) was not significantly higher than the correlation between TBW (D2O dilution) and WB BIA measures (simple regression, r = 0.85, p < 0.001, SEE = 3.6 L). Others have observed this "lack of improvement" in a group of healthy subjects. The true value of the segmental BIA methodology may lie in applications involving groups with altered distributions of segmental and compartmental fluid.

Adult↗

Modeling leg sections by bioelectrical impedance analysis, dual-energy X-ray absorptiometry, and anthropometry: assessing segmental muscle volume using magnetic resonance imaging as a reference.

This study aimed to assess the value of different DXA and BIA models for predicting muscle volume in mid-thigh segments obtained by MRI. Three DXA models were used: in model A, muscle was taken to be equivalent to fat-free soft tissue; in model B the thigh segment was divided into its constituent tissues using fixed assumptions about tissue composition; in model C the assumptions were similar to model B, but with variable distribution of fat and fat-free soft tissue, depending on body mass index. The two BIA models (both parallel tissue resistance models) involved impedance measurements at 50 kHz, and assumptions about either the specific resistivities of all the constituent tissues (model A), or resistivities of only adipose tissue and muscle (model B). Anthropometric estimates (thigh circumference and skinfold thickness) assumed that both limb and muscle circumference were circular. Compared to MRI estimates of muscle mass, those obtained by DXA model A (fat-free soft tissue) were not as good as those obtained using models B and C, although the standard deviations of the differences were similar with all three models. The BIA models were superior to the anthropometric estimates of muscle volume (relative to MRI) with respect to bias, but the standard deviations of the differences were large for both. The intraobserver repeatabilities for muscle volume were < 0.5% for MRI, < 1% for DXA, 1.8% for BIA, and 1.7% for anthropometry (interobserver value for BIA was 3.8% and for anthropometry 3.5%). The study suggests that DXA modeling provides a promising approach for assessing muscle mass in thigh segments, and suggests the potential value of parallel BIA models for groups of individuals but not for individual subjects, possibly because muscle resistivity is influenced not only by its composition but also by the direction of current flow in muscle.

Absorptiometry, Photon↗

Early diagnosis of lymphedema in postsurgery breast cancer patients.

Lymphedema is an accumulation of lymph fluid in the limb resulting from an insufficiency of the lymphatic system. It is commonly associated with surgical or radiotherapy treatment for breast cancer. As with many progressively debilitating disorders, the effectiveness of treatment is significantly improved by earlier intervention. Multiple frequency bioelectrical impedance analysis (MFBIA) previously was shown to provide accurate relative measures of lymphedema in the upper limb in patients after treatment for breast cancer. This presentation reports progress to date on a three-year prospective study to evaluate the efficacy of MFBIA to predict the early onset of lymphedema in breast cancer patients following treatment. Bioelectrical impedance measurements of each upper limb were recorded in a group of healthy control subjects (n = 50) to determine the ratio of extracellular limb-fluid volumes. From this population, the expected normal range of asymmetry (99.7% confidence) between the limbs was determined. Patients undergoing surgery to treat breast cancer were recruited into the study, and MFBIA measurements were recorded presurgery, at one month and three months after surgery, and then at two-month intervals for up to 24 months postsurgery. When patients had an MFBIA measure outside the 99.7% range of the control group, they were referred to their physician for clinical assessment. Results to date: Over 100 patients were recruited into the study over the past two years; at present, 19 have developed lymphedema and, of these, 12 are receiving treatment. In each of these 19 cases, MFBIA predicted the onset of the condition up to four months before it could be clinically diagnosed. The false-negative rate currently is zero. The study will continue to monitor patients over the remaining year to accurately ascertain estimates of specificity and sensitivity of the procedure.

Adult↗