Mucins and CD56 as markers of tumour invasion and prognosis in periampullary cancer.

BACKGROUND: This study investigated the association of mucins and cluster of differentiation (CD) 56 with vascular and perineural invasion and survival in patients with periampullary cancer. METHODS: Immunohistochemical staining was performed on formalin-fixed pancreatic tissue microarrays (cancer, chronic pancreatitis and normal pancreatic tissue) constructed from 126 pancreatic resections (cancer, 104; chronic pancreatitis, 22). Mucin (MUC) 1, MUC4 and MUC5AC expression was quantified using the immunohistochemical score (range 0-300), MUC3 expression was described as membranous or cytoplasmic, and expression of CD56, MUC2 and MUC6 as present or absent. RESULTS: In cancers, vascular invasion correlated with overexpression (immunohistochemical score of 100 or more) of MUC1 (P = 0.003) and presence of MUC6 (P = 0.024), and perineural invasion correlated with overexpression of MUC5AC (P = 0.015). Reduced survival was observed with overexpression of MUC4 (P = 0.032) and MUC5AC (P = 0.048), membranous expression of MUC3 (P = 0.048), and presence of CD56 (P = 0.041). Perineural invasion also correlated with CD56 expression (P = 0.001). Overexpression of MUC4 and MUC5AC correlated with tumour recurrence (P = 0.001 and P = 0.034 respectively). Multivariable analysis identified membranous expression of MUC3 (P = 0.023), lymphatic invasion (P = 0.015) and perineural invasion (P = 0.004) as independent predictors of poor survival. CONCLUSION: Mucins and CD56 may be markers of prognosis in patients with periampullary cancer.

The effect of jaundice on the generation of anti-gastrin antibodies in G17DT immunized patients with advanced pancreatic cancer.

AIM: The aim of this study was to determine the ability of G17DT to generate anti-gastrin antibodies in jaundiced patients with biliary obstruction due to advanced pancreatic cancer. METHODS: G17DT was administered to 41 patients with advanced pancreatic adenocarcinoma by intramuscular (i.m.) injection at a dose of 250mcg at weeks 0, 1 and 3 of the study. RESULTS: Thirty-five of 41 patients participating in the study were categorized as responders in terms of their gastrin-17 antibody response. There was no correlation between the maximum G17 antibody response and the bilirubin level at either week 0 or week 12. The median survival of patients from the time of the first injection of G17DT was 204 days with 25% of patients surviving for or=305 days. CONCLUSION: This study shows that G17DT administered to jaundiced patients with advanced pancreatic cancer is immunogenic and well tolerated.

Inhibition of matrix metalloproteinase activity and growth of gastric adenocarcinoma cells by an angiotensin converting enzyme inhibitor in in vitro and murine models.

INTRODUCTION: Angiotensin converting enzyme (ACE) shares structural homology with the matrix metalloproteinase family of proteolytic enzymes (MMPs) responsible for degradation of the extracellular matrix (ECM). ACE inhibitors have been reported to protect against cancer in patients. The aim of this study was to determine whether the ACE inhibitor, captopril, could impair the activity of MMPs and impact on tumour invasion and growth in a cell line and murine model. METHODS: For proof of principle, the protein activity of human MMP-2 and MMP-9 produced by the HT1080 fibrosarcoma cell line was detected using gelatin zymography. Gene expression was determined by real time reverse transcriptase PCR and tumour cell invasion using Matrigel invasion chambers. The effect of captopril on the in vivo growth of MGLVA-1 human gastric adenocarcinoma xenografts was evaluated in a nude mouse model. RESULTS: Captopril inhibited activity of secreted MMP-9 and MMP-2, however, gene expression in HT1080 remained unaltered. Invasion of HT1080 cells was inhibited by 48% (p<0.001). Tumour size was reduced by 40-50% with 0.4 mg/ml captopril (p<0.01) and when combined with cisplatin the inhibition increased to 71% (p<0.05). DISCUSSION: ACE inhibitors inhibit the activity of secreted MMP-2 and -9 by a mechanism similar to synthetic MMP inhibitors. ACE inhibitors have previously been shown to inhibit tumour growth, however; this is the first study to demonstrate inhibition of a human gastric xenograft, both alone and in combination with cisplatin. These results support further investigation into the anticancer effects of ACE inhibitors.

A practical posture for hand grip dynamometry in the clinical setting.

BACKGROUND & AIMS: The optimal testing position for hand grip strength, which is a useful functional measure of nutritional status, is open to debate. We therefore examined the systematic difference between different postures in order to establish a methodology that is clinically relevant, easy to perform and reproducible. METHODS: Grip strength was measured in the dominant and non-dominant hands with a strain gauge dynamometer in three positions: lying at 30 degrees in bed with elbows supported, seated in an armchair with elbows supported and in a chair with elbows unsupported. The average of three readings made in each position, each 1 min apart, was recorded. RESULTS: 55 normally nourished subjects (26 male) were studied. Mean (95% CI) grip strengths measured in the dominant hand with the subject in bed, sitting in an armchair and sitting in a chair were 45.7 (42.3-49.2), 46.3 (42.9-49.8) and 48.5 (45.4-51.7) kg, respectively for males. Corresponding values for females were 29.4 (27.0-31.8), 29.3 (26.8-31.9) and 31.6 (28.8-34.3) kg. There was no significant difference (Student t-paired test) between measurements made in bed and on an armchair (P = 0.49), but the measurements made in a chair were significantly higher than those made in bed (P = 0.001) and in an armchair (P = 0.004). No statistical difference was present, comparing the three separate measurements in each position (Student t-paired test). CONCLUSIONS: Measurement of grip strength using hand dynamometry is reproducible and consistent. As all patients are not able to sit in a chair with elbows unsupported, in clinical practice it is more practicable to perform hand dynamometry with the elbows supported in a bed or armchair.

Relationships between structural and functional measures of nutritional status in a normally nourished population.

BACKGROUND AND AIMS: Both anthropometric and functional measurements have been used in nutritional assessment and monitoring. Hand dynamometry is a predictor of surgical outcome and peak expiratory flow rate has been used as an index of respiratory muscle function. This study aims to measure in normal subjects the relationship between anthropometric measurements, voluntary muscle strength by hand grip dynamometry and respiratory muscle function by peak expiratory flow rate. METHODS: Ninety-eight subjects (46 male, 52 female) with a mean age of 45.9 years were studied. Hand grip strength was measured in the dominant and non-dominant hands with a portable strain-gauge dynamometer. Peak expiratory flow rate was measured using a mini-Wright peak flow meter. Three readings were taken, each 1 min apart, and the average recorded. Midarm muscle circumference (MAMC) was derived from triceps skin fold thickness and midarm circumference (MAC) using standard anthropometric techniques. Statistical relationships were measured with Pearson's coefficient of correlation. RESULTS: In both sexes there was significant correlation between hand grip strength in the dominant and non-dominant hands and peak expiratory flow rate (P<0.001). In men, there was a positive correlation between MAMC, hand grip strength (P<0.001) and peak expiratory flow rate (P<0.001). In women muscle function correlated with height (P<0.001) but not MAMC (P>0.05). CONCLUSIONS: In normal subjects bedside tests of skeletal and respiratory muscle function correlated with each other in both sexes, and with muscle mass in men but not in women.

Changes in nutritional status associated with obstructive jaundice and biliary drainage in rats.

Effect of bile duct ligation (BDL) and internal biliary drainage on food intake and nutritional status was studied in rats and compared with sham and pair-fed animals. During week 1, food intake of BDL animals was reduced (p less than 0.05), resulting in weight loss (p less than 0.05). In weeks 2 and 3, food intake, nitrogen balance, and weight gain were similar in all groups. Internal biliary drainage or sham operation after 3 wk produced transient changes in food intake and N2 balance. Serum albumin fell in all groups, returned to normal in sham (3.2 +/- 0.1 g/dl) and pair-fed (3.1 +/- 0.1 g/dl), but persisted in BDL rats (2.4 +/- 0.2 g/dl, p less than 0.001). Jaundice was associated with anemia. Although BDL produces transient changes in food intake, weight gain, and N2 balance, anorexia and malnutrition are not features of this animal model. Nutritional risk factors associated with hyperbilirubinemia are probably due to changes in intermediary metabolism.

Development and reversal of endotoxemia and endotoxin-related death in obstructive jaundice.

Gut-derived endotoxemia has been implicated in postoperative complications in patients with jaundice. It is thought that absence of bile in the gut predisposes to portal absorption of endotoxin and endotoxemia is reversed by oral bile salt replacement or internal biliary drainage and return of bile to the gut, but not by external drainage. We believe that the importance of gastrointestinal bile flow has been overestimated and biliary obstruction and the integrity of hepatocyte and Kupffer cell function are more important in the development and reversal of endotoxemia. In experiment 1, serum endotoxin concentrations were measured in control rats (n = 10) after choledochovesical fistula (n = 15) and bile duct ligation (n = 15) and after relief of biliary obstruction by internal drainage (choledochoduodenostomy; n = 8) and sterile external drainage (choledochovesical fistula; n = 8), with a quantitative limulus assay. In experiment 2, mortality rates were measured in similar groups 48 hours after administration of oral endotoxin (5 mg/100 gm) and intravenous lead acetate (5 mg/100 gm). Bilirubin levels were elevated in bile duct ligation (192 +/- 13 mumols/L) compared with control animals and those with choledochovesical fistula, internal drainage, and external drainage (10.6 +/- 1.5 mumols/L). In experiment 1, significant portal endotoxemia and systemic endotoxemia occurred in bile duct ligation (portal, 130.4 +/- 12.9 pg/ml; systemic, 91.8 +/- 11.0 pg/ml) but not in choledochovesical fistula (portal, 49.3 +/- 17.1 pg/ml; systemic, 27.2 +/- 11.5 pg/ml). Relief of obstruction by both internal and external drainage reversed endotoxemia. In experiment 2, significant death occurred in bile duct ligation (13 of 15) but not in choledochovesical fistula (3 of 15), and relief of obstruction by both internal and external drainage prevented death. These results confirm that biliary obstruction is a more important factor than is gastrointestinal bile flow in the development and reversal of endotoxemia.

Selective decontamination of the digestive tract: a stratified, randomized, prospective study in a mixed intensive care unit.

To evaluate the use of selective decontamination of the digestive tract (SDD) (polymyxin, amphotericin, tobramycin, and intravenous cefotaxime) in a mixed intensive care unit, we performed a stratified, randomized, prospective study. The 331 patients were recruited over an 18-month period, with 256 patients remaining more than 48 hours. Stratification by acute physiology and chronic health evaluation (APACHE II) preceded randomization to control (standard antibiotic therapy) or treatment (SDD) groups. Nosocomial infection was significantly reduced in the SDD group (16.7%; 21 of 126 patients) compared with the control group (30.8%; 40 of 130 patients; p = 0.008). No difference was found in overall mortality rate or length of stay between the two groups. Those patients with admission APACHE II scores 10 to 19 demonstrated the most significant reduction in nosocomial infection (23 of 70 control vs 13 of 76 SDD; p = 0.03) and mortality (15 of 70 control vs 8 of 76 SDD; p = 0.07). Emergence of multiresistant microorganisms was not a clinical problem, but a definite change occurred in the ecology of environmental and colonizing bacteria. With the exception of cefotaxime, a reduction was noted in systemic antibiotic usage in the SDD group. We conclude that SDD is useful in selected patients in a mixed intensive care unit.

The influence of hepatocellular function on NK and T cell tumoricidal activity.

Recent studies by this group have demonstrated that hepatocellular integrity is important in the preservation of host cellular immune function. This study evaluated the effect of experimental hepatocellular dysfunction (EHD) on host antineoplastic defense mechanisms. In nonspecific immune studies, we examined the effect of EHD on Wistar Furth (WF) natural killer (NK) cell cytotoxicity; in specific immune studies, we assessed WF C3H/HeJ lymphocytic responsiveness to both T cell mitogen and unmodified syngeneic fibrosarcoma. In concurrent studies, we evaluated the effect of EHD on interleukin-2 (IL-2) synthesis, an important NK and T cell trophic factor. WF rats and C3H/HeJ mice were assigned to three groups: EHD induced by bile duct ligation, sham, and normal control (NC). At day 21 serum bilirubin, WF NK cytotoxicity to YAC-1 tumor cells, WF and C3H/HeJ lymphocytic responsiveness to phytohemagglutinin (PHA) and syngeneic MCA-fibrosarcoma (MCA-F), and WF T-helper IL-2 production were determined in respective groups. Serum total bilirubin was elevated in EHD rats and mice with respect to controls (p less than 0.01). Wistar Furth cytotoxicity to the YAC-1 tumor cells was depressed in EHD animals with respect to sham and NC groups at 12.5:1 (p less than 0.01), 25:1 (p less than 0.05), 50:1 (p less than 0.05), and 100:1 (p less than 0.05) effector/target cell ratios. WF T cell responsiveness to PHA was depressed in EHD with respect to controls (p less than 0.01). C3H/HeJ lymphoproliferative response to MCA-F tumor antigen was also depressed in EHD animals when compared with control groups with the addition of 12.5 X 10(3) (p less than 0.05) and 50 X 10(3) (p less than 0.05) MCA-F cells. These impairments in NK and T cell function in EHD could not be attributed to diminished IL-2 production (EHD vs sham and NC: 112,141 +/- 5232 vs 106,691 +/- 1419 and 120,759 +/- 3248 cpm, respectively). These results demonstrate that hepatocellular failure compromises NK and T cell tumoricidal function, an effect not resultant on diminished T helper IL-2 production.

Single-dose intraoperative antibiotic prophylaxis in emergency abdominal surgery.

In a randomized controlled trial of the use of a single intravenous dose of gentamicin sulfate and clindamycin phosphate used intraoperatively during emergency abdominal surgery, the overall incidence of postoperative wound infection was reduced from 32.3% to 10.4%. Significant reduction in wound infection occurred in the study group compared with control subjects irrespective of the underlying pathologic lesion. No side effects of the use of antibiotics were noted. The policy of antibiotic prophylaxis in emergency surgery seems to be of particular benefit in elderly patients.

Effects of extrahepatic obstructive jaundice on Kupffer cell clearance capacity.

Systemic endotoxemia consistently occurs in jaundiced patients undergoing surgery. Kupffer cell dysfunction is implicated in the development of endotoxemia and its postoperative complications. A novel in situ single-pass hepatic perfusion technique using a fluorescein isothiocyanate-labeled latex probe was developed for measuring Kupffer cell clearance capacity and was applied in an animal model of biliary obstruction. Control rats and rats jaundiced for 1, 2, 3, and 4 weeks' duration were studied. Kupffer cell clearance capacity, plasma bilirubin, endotoxin, and anticore glycolipid concentrations were measured. Maximal hyperbilirubinemia preceded reduced Kupffer cell clearance capacity. Rats jaundiced for greater than 2 weeks had a significantly decreased Kupffer cell clearance capacity but significantly higher endotoxin and anticore glycolipid concentrations. Anticore glycolipid concentrations correlated strongly with systemic endotoxemia and both were inversely correlated with duration of jaundice. Impairment of Kupffer cell clearance capacity may contribute to endotoxemia associated with cholestasis.

Jass' classification revisited.

BACKGROUND: In 1986, Jass and colleagues claimed to have improved on Dukes' classification of prognosis for carcinoma of the colon and rectum. To have clinical relevance, such results should be reproducible and confirmed by other institutions. STUDY DESIGN: Retrospective clinicopathologic study of 312 carcinomas of the colon and rectum to determine whether or not Jass' classification is superior to that of Dukes' as assessed by their relative reproducibility and prognostic significance. RESULTS: Dukes' classification had excellent intraobserver and interobserver reproducibility (kappa values of 0.86 and 0.93, respectively). In contrast, the reproducibility of variables assessed by Jass showed only slight to fair agreement (lymphocytic infiltration: intraobserver and interobserver kappa values of 0.08 and 0.05, respectively, growth pattern: intraobserver and interobserver kappa values of 0.37 and 0.41, respectively). Dukes' stage and patient age were the most important prognostic variables on multivariate regression analysis. Tumor differentiation, nuclear polarity, tubule configuration, and lymphocytic infiltration remained significantly related to survival in the presence of Dukes' stage and age. The model which best predicted prognosis was a combination of Dukes' stage, patient age and tumor differentiation. Further addition of the variables assessed by Jass to this model did not significantly improve the prediction of prognosis. CONCLUSIONS: Dukes' classification is of greater prognostic value and more reproducible than the components of Jass' classification. The continued use of Dukes' classification is, therefore, warranted for prognostic and therapeutic decisions in patients with carcinoma of the colon and rectum.

Epidemiology of Pseudomonas aeruginosa in an intensive care unit using selective decontamination of the digestive tract.

Selective decontamination of the digestive tract (SDD) aims to reduce the rate of nosocomial infections in critical care patients. Pseudomonas spp. are common nosocomial pathogens and in this study isolates collected from patients and the environment during an SDD trial were examined. The study enrolled 161 SDD cases and 170 controls. Pseudomonads were isolated from 27% of SDD patients and 30% of controls. SDD partially suppressed colonization in the 'gastro-respiratory' mucosae but not in the rectum. A total of 108 isolates of pseudomonads were recovered from the environment. Resistance in rectal isolates was minimal but isolates from 'gastro-respiratory' sites showed increasing aminoglycoside resistance. Eighty-six per cent of aminoglycoside-resistant isolates from both patient groups and environment were pyocine type 1x. Episodes of infection were reduced in the SDD patients (6) compared with the controls (16), aminoglycoside-resistant strains being associated with zero episodes in SDD patients but with five in the control group.

Glucose and insulin homeostasis during postoperative carbohydrate infusions.

Hypertonic fructose and sorbitol solutions are claimed to have advantages over glucose in nutritional regimen due to their rapid hepatic metabolism. Insulin is essential for the extrahepatic metabolism of all three carbohydrates. At therapeutic rates (0.5 g/kg body weight/h) in the postoperative period they produce hyperglycaemia and an insulin response, not previously evident and similar to that of glucose. These changes are probably related to their intracellular metabolism and may explain the similar nitrogen-sparing capabilities of each carbohydrate following operative trauma.

An ELISA for measuring tumour necrosis factor alpha in rat plasma.

Tumour necrosis factor (TNF) is a cytokine with multiple biological activities which plays a pivotal role in the response of the body to infection. TNF is secreted in the the monomeric form and associates to yield a biologically active oligomeric molecule. Bioactive TNF can be measured in plasma using cytotoxic assays which employ the murine cell-lines L929 or WEHI 164 clone 13. However, it has become clear that inactive TNF also circulates in vivo, which is not detected by bioassay. These inactive forms may play an important role in the regulation of TNF activity. The rat is often used as a model for the study of acute infection and its systemic effects. Our aim was to develop an ELISA for rat TNF which would provide a convenient and cost effective method of assay. The assay employs two commercially available antibodies raised against recombinant murine TNF (rMuTNF) which exhibit cross-reactivity with rat TNF. The lower limit of detection for this assay was determined to be 39.0 pg/ml rMuTNF. The inter and intra-assay coefficients of variation were < 12.0%. Specificity of the assay was shown by the high degree of parallelism obtained between rMuTNF and commercially available rRatTNF. The assay described measures rat TNF in both plasma and tissue culture supernatant. The measurement of plasma concentrations of TNF using both the ELISA and bioassay may help elucidate more fully the biological importance of TNF.

General metabolism in patients with acute paraplegia and quadriplegia.

This study measured the nutritional status of eight spine-injured patients during their first 10 to 14 days in the hospital. Initial and follow-up nutritional assessment showed that their nutritional status deteriorated at least partly due to an inadequate supply of protein and calories. Infective complications and prolonged respiratory support were common and may have been caused in part by impaired nutrition. This suggests that a prospective study of aggressive nutritional support for patients with spinal cord transection should be initiated to determine whether this acquired malnutrition and its associated complications can be prevented.

General metabolism in head injury.

Seventy-six patients with closed head injuries alone were studied to define the relation between the severity of the head injury and secondary alterations of general metabolism. The effect of metabolic changes on neurological outcome and the importance of nutritional support on nutritional status and neurological outcome were also evaluated. Using a powerful statistical tool, convergence analysis, it was possible to take into consideration the effects of a number of confounding factors that obviously affected general metabolism. Most of the patients were hypermetabolic for prolonged periods. In addition, many did not receive even basal requirements of calories or protein for many days. Despite this, their outcomes were determined by their initial neurological status and the amounts that they were fed, admittedly relatively modest, did not influence their courses. Despite such feedings, their visceral protein levels, which often dropped initially, rose toward normal levels, indicating effective adaptation. Indeed, it could not be shown that these patients developed complications of malnutrition such as infections. However, it will require a sophisticated randomized clinical trial of vigorous intravenous hyperalimentation to determine whether this complex, dangerous, and expensive therapy is helpful for severely head-injured patients.

The 'two-week' target for the diagnosis of pancreatic carcinoma: an achievable aim?

AIM: The aim of this study was to evaluate the current diagnostic process for patients with pancreatic cancer in a University teaching hospital and to determine whether the 'two-week' target for rapid assessment was being met. METHODS: The notes of all patients with pancreatic cancer from June 1998 to June 2000 were reviewed to determine the time to diagnosis, investigations and procedures performed, number of admissions, length of hospital stay and survival RESULTS: There were 146 patients in total with a median (range) age of 71 (38-92) years. 18 (12%) had resectable lesions, while the remaining 128 patients had 134 palliative interventions (33 surgical; 101 radiological or endoscopic). The median number of hospital admissions for each patient was 2 (range 1-6) with a median length of hospital stay of 9 days (range 1-35 days). The median (IQR) time to diagnosis was significantly less in the jaundiced patients [7 (6-10) days vs. 32 (18-46) days, P<0.0001]. There was no significant correlation between age and time to diagnosis (r=0.08, P=0.36). There were 105 (72%) deaths in the study population, 82 in the jaundiced group and 23 in the non-jaundiced group. There was no significant difference in median (IQR) duration from referral to death in the jaundiced and non-jaundiced groups [59.5 (18-175) days vs. 35 (16-137) days, P=0.45]. CONCLUSIONS: A diagnosis within 14 days was achieved in 77% of patients. Patients with jaundice were more likely to have an earlier diagnosis than those without jaundice but this had no impact on survival.

Changes in weight, fluid balance and serum albumin in patients referred for nutritional support.

BACKGROUND AND AIMS: Starvation and injury impair the excretion of an excess sodium and water load, resulting in oedema and hypoalbuminaemia, which may have adverse effects on gastrointestinal physiology. We have retrospectively assessed clinical signs and fluid balance in 44 adult patients referred for nutritional support for >== 10 days. METHODS: Clinical evidence of oedema was noted. Oedematous patients were managed with a low sodium (0-50 mmol/day), low volume (2 l/day) feed. Some also received albumin and a diuretic. Body weight was recorded daily and serum albumin three times weekly. The lowest recorded weight during nutritional support and the weight at the time of discharge were correlated with serum albumin concentration. RESULTS: The 21 patients with oedema had acute surgical conditions and complications such as sepsis while the 23 non-oedematous patients had chronic conditions with gradual nutritional depletion. During nutritional support the mean (SEM) weight in kg of the oedematous patients fell from 79.3 (2.9) to 69.2 (3.2) (P>> 0.00001) and subsequently rose to 70.1 (3.2) (P= 0.005). Corresponding values for the non-oedematous patients were 61.4 (4.0), 60.2 (3.9) (P>> 0.05) and 61.2 (3.7) (P= 0.002) respectively. Weight reduction reflected negative salt and water balance and correlated with a rise in serum albumin (r = -0.61 for oedematous and r = -0.65 for non-oedematous patients) largely reflecting reversal of previous dilution. CONCLUSION: These findings have important implications for the salt and water content of perioperative fluid and nutritional prescriptions. They also emphasize the dilutional component of hypoalbuminaemia in these patients.

Body water compartment measurements: a comparison of bioelectrical impedance analysis with tritium and sodium bromide dilution techniques.

BACKGROUND AND AIMS: This study was undertaken to assess the comparability of body water compartment estimates in healthy volunteers using single and dual frequency bioelectrical impedance analysis (BIA) with established reference methods of tritium and NaBr dilution. METHODS: Total body water (TBW) was estimated in 10 healthy volunteers using single frequency (50 kHz) BIA (Bodystat 1500), dual frequency (5 and 200 kHz) BIA (Bodystat Dualscan 2005) and tritium dilution. Extracellular water (ECW) was measured with dual frequency BIA and NaBr dilution. BIA was performed using distal tetrapolar electrodes in the supine position. Venous blood was sampled for measurement of background concentrations of tritium and NaBr using a beta counter and high performance liquid chromatography respectively. 10 ml tritiated water (3.7 MBq) and 50 ml 5% NaBr solution were then injected intravenously and blood samples taken from the opposite arm every 45 min for 4.5 h for estimation of concentrations of tritium and NaBr. RESULTS: There was good correlation (r(2)=0.76) between estimates of ECW using dual frequency BIA and NaBr dilution, with the former overestimating ECW by approximately 1 L. However, this difference varied systematically with body weight. Although TBW measurements obtained by single and dual frequency BIA correlated well with estimates using tritium dilution (r(2)=0.96 and 0.95 respectively), single frequency BIA underestimated TBW by approximately 1 L and dual frequency BIA by approximately 5 L compared to tritium dilution. CONCLUSION: TBW measurements obtained using the single frequency BIA device were more accurate than those obtained using the dual frequency BIA device. Dual frequency BIA provided a reasonably accurate estimate of ECW.