Aminophylline loading in asthmatic patients: a protocol trial

We tested an aminophylline loading-dose protocol in which asthmatic patients presenting to an emergency department were given a half (3 mg/kg) IV loading dose based on total body weight (TBW) if they had taken a short-acting or sustained-release theophylline preparation within 12 or 24 hours, respectively, prior to arrival: otherwise, a full (6 mg/kg) loading dose was administered. Of the 28 patients given a full loading dose, 20 (71.4%) achieved a postload therapeutic level (10 to 20 micrograms/mL), and none developed a toxic level (greater than 20 micrograms/mL). Although 34 (60.7%) of 56 patients given a half loading dose attained a postload therapeutic level, 13 patients (23.2%) entered the toxic range. We were able to predict that loading doses of 7.6 mg/kg and 3.8 mg/kg based on ideal body weight (IBW) would have yielded very similar results. The mean change in theophylline level per mg/kg TBW of administered aminophylline was 2.01 micrograms/mL. When calculated on the basis of IBW, the mean change in theophylline level was 1.58 micrograms/mL. Evaluation of the change in theophylline level resulting from aminophylline loading doses based on either TBW or IBW revealed that each dosing method produced changes in blood level with similar variability that were not independent of obesity, indicating that neither dosing method is superior to the other. Thus, patients who report not having taken a theophylline preparation within the above time limits can be given a full aminophylline loading dose of either 6 mg/kg based on TBW or 7.6 mg/kg based on IBW. Other patients, however, require a preload blood level determination to optimize therapy and avoid toxic levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Volume of distribution of theophylline in acute exacerbations of reversible airway disease. Effect of body weight

The literature is unclear as to whether theophylline loading doses should be based on total body weight (TBW) or ideal body weight (IBW). The objective of this study was to determine the most appropriate body weight for estimation of volume of distribution (Vd) in calculating theophylline loading dose in patients with acute bronchospasm. Fifty-four adult patients with acute bronchospasm requiring intravenous (IV) theophylline therapy were entered into the study. Patients were randomized into three theophylline loading dose groups based on (1) TBW, (2) IBW, and (3) adjusted body weight (ABW). Initial serum theophylline concentrations were used to determine an IV loading dose to reach a plasma concentration of 12 to 15 micrograms/ml. Percent prediction error was used to determine the appropriateness of each dosing group. Volumes of distribution were also determined for each group. There was a statistically significant difference at p less than 0.01 in the percent prediction error when patients in the TBW group were compared to the IBW and ABW groups. A statistically significant difference in the Vd was observed between the TBW and IBW group (p less than 0.01). We conclude that IBW is more appropriate than TBW or ABW for determining theophylline loading dose in patients with acute bronchospasm.     

Dual-energy X-ray absorptiometry is the method of choice to assess body composition in COPD

Background and objective:   Mortality and morbidity in COPD have been related to reduced FEV₁ as well as indices of body composition. Different techniques used to evaluate body composition may vary in accuracy, particularly in conditions with altered fluid balance such as COPD. We hypothesized that direct measurement of fat-free mass index (FFMI) by dual-energy X-ray absorptiometry (DEXA) would provide superior assessment of body composition in COPD.
Methods:   We measured body composition in 31 patients with COPD randomly selected from a teaching hospital clinic. To estimate total body water (TBW) and FFMI, skin-fold anthropometry, bioelectrical impedance analysis (BIA) with Schols and Lukaski equations as well as DEXA, total body potassium by whole-body γ-counting (TBK) and in vivo neutron activation analysis were used. Combined body composition methods providing precise estimations of TBW were used for comparisons. Bland–Altman analyses, ANOVA and χ²-testing were used to examine data.
Results:   Mean BMI was 27.6 ± 5.34 kg/m² (mean ± SD). Estimations of TBW were similar using Schols BIA or by using combined body composition methods. FFMI did not vary significantly between grades of COPD severity but was significantly different when assessed using DEXA and other methods. Calculated FFM hydration was significantly different from the fixed hydration factor used to calculate FFMI from BIA TBW ( P  < 0.05).
Conclusion:   The Schols BIA method incorporates a fixed hydration factor that may lead to an erroneous estimation of FFMI with ensuing clinical implications. DEXA can be used to obtain accurate and comprehensive assessments of body composition and should be the preferred investigation in COPD.     

The impact of new comorbidities on nutritional status in continuous ambulatory peritoneal dialysis patients

OBJECTIVE: To study the prevalence and risk factors for malnutrition in a peritoneal dialysis (PD) center with an active PD program. METHODS: We assessed the nutritional status in 205 continuous ambulatory peritoneal dialysis (CAPD) patients, including stable and unstable patients, by subjective global assessment (SGA), dietary diaries and biochemistry index. Serum C-reactive protein (CRP) levels were examined as inflammatory marker. Fluid status including extracellular water (ECW), intracellular water, and total body water (TBW) was evaluated by multiple-frequency bioelectrical impedance analysis and brachial blood pressure was measured. New comorbidities included systemic infection, congestive heart failure and trauma that occurred within 1 month or less. Cardiovascular disease (CVD) was recorded too. Dialysis adequacy and residual renal function were calculated by a standard technique. RESULTS: Based on SGA, 15.6% of our CAPD patients were malnourished. The malnourished patients had advanced age, higher CRP and ECW/TBW levels than normally nourished patients (age: 68.78 +/- 11.92 vs. 59.26 +/- 13.46 years, p = 0.001; CRP: 11.98 +/- 20.22 vs. 5.56 +/- 8.30 mg/l, p = 0.004; ECW/TBW: 0.55 +/- 0.16 vs. 0.52 +/- 0.04, p = 0.049). Patients with malnutrition were more prone to have CVD (53.13 vs. 31.79%, p = 0.004) and new comorbidities (65.62 vs. 4.62%, p = 0.023). Multivariate analysis showed new comorbidities, mostly systemic infection, which were associated with nutritional status (p < 0.001). Both ECW/TBW and new comorbidities were associated with serum CRP, CVD and malnutrition (p < 0.001-0.05). In contrast, some traditional factors which were recognized as contributing to malnutrition such as residual renal function, dialysis adequacy, metabolic acidosis, total protein loss, diabetes and Charlson indexes were not different between normally nourished and malnourished patients in the present study. CONCLUSIONS: Our results suggest that only 15.6% of patients were malnourished in our PD program. Old age, inflammation, CVD, fluid overload and new comorbidities were all associated with malnutrition, with new comorbidities, mostly systemic infections, being the most significant risk factor. However, many traditional factors such as residual renal function, dialysis adequacy and diabetes were not.     

Intravenous unfractionated heparin dosing in obese patients using anti-Xa levels

There is limited guidance on intravenous dosing of unfractionated heparin in obese patients. The purpose of this study was to determine the efficacy and safety of a standard unfractionated heparin (UFH) protocol in obese patients based on total body weight (TBW) or adjusted body weight (ABW) to reach two consecutive therapeutic anti-Xa levels. This was a retrospective observational cohort study conducted in a large academic medical center. Adults received a standard UFH protocol between January 1, 2013 to December 31, 2015. Inclusion criteria included age ≥ 18 years of age, weight ≥ 100 kg with a BMI ≥ 30 kg/m², and received intravenous UFH. Patients were excluded if they received an alternative UFH protocol, received?<?24 h of the standard UFH protocol, or had inadequate compliance to protocol. Out of the 131 patients included, 109 patients reached two consecutive therapeutic UFH levels within 96 h. The average time to two consecutive therapeutic UFH levels was 29.4 h and 27.6 h in patients dosed by TBW and ABW, respectively (95% CI ??4.63 to 8.11; P?=?0.93). Safety outcomes included major bleeding, overt bleeding, or death events between patients dosed by TBW compared to ABW, (p?=?0.61, p?=?1.0, p?=?1.0, respectively). Dosing intravenous UFH based on TBW or ABW resulted in similar times to therapeutic anti-Xa levels and safety outcomes. The data provided suggests using either TBW or ABW in obese patients is as effective and safe to use.

     

Presence of carpal tunnel syndrome in diabetics: Effect of age,sex, diabetes duration and polyneuropathy

Summary Common thought is that diabetic neuropathy is a predisposing factor to entrapment syndromes. Carpal tunnel syndrome (CTS) is the most frequent entrapment neuropathy; females and old people are most frequently affected (Comi et al., 1978). Prevalence of CTS in diabetics and associated risk factors were studied in 401 patients (208 males and 193 females) with insulin-dependent and non-insulin-dependent diabetes using electrophysiological techniques. Median nerve sensory and motor conduction velocity, ulnar and peroneal nerve motor conduction velocity and sural nerve sensory conduction velocity were investigated in all patients. Diagnostic criteria for CTS were the presence of delayed median nerve sensory conduction velocity in the palm-wrist tract and of increased distal motor latency. Polyneuropathy was defined by slowing-down of conduction velocity in two or more nerves. Forty-five patients (11.2%), 36 females and 9 males, showed CTS. One-hundred-sixty-eight patients (41.8%), 74 females and 94 males, were suffering from peripheral neuropathy. The strongest risk factors for CTS, in order of importance, were: female sex, older age and presence of neuropathy. Polyneuropathy but not CTS was related to duration of diabetes.     

Bioelectrical impedance analysis estimation of water compartments in elderly diseased patients: the source study

BACKGROUND: This study validates, in geriatric patients, bioelectrical impedance analysis (BIA) equations that had been derived to estimate total body water (TBW) and extracellular water (ECW) in healthy elderly subjects. METHODS: We performed a multicentric trial in six geriatric wards. We studied 169 patients with varying degrees of hydration: dehydrated, euvolemic, and overhydrated. BIA estimates of TBW and of ECW were compared with the measurement of TBW with (18)O dilution and of ECW with bromide (Br) dilution. RESULTS: BIA estimated TBW with a difference of 0.48 +/- 2.3 l (mean +/- SD) (50 kHz; p = .01) and 0.69 +/- 2.2 l (100 kHz; p < 0.001) compared with (18)O dilution. The difference was not affected by the hydration status. Estimates of ECW with BIA were systematically biased compared with Br dilution: 4.6 +/- 3.1 l (equation from Segal and colleagues; p < .001) and 3.4 +/- 2.9 l (equation from Visser and colleagues; p < .001). We propose a new, cross-validated equation. Conclusions. Body water spaces can be estimated accurately in geriatric patients with BIA.     

Increased major bleeding complications related to triple antithrombotic therapy usage in patients with atrial fibrillation undergoing percutaneous coronary artery stenting

BACKGROUND: The optimal antithrombotic therapy strategy for atrial fibrillation (AF) patients who undergo percutaneous coronary intervention with stent implantation (PCI-S) is unknown. We assessed the safety of antithrombotic therapy strategies in AF patients with indication for oral anticoagulation (OAC) undergoing PCI-S. METHODS: We studied consecutive AF patients with indication for OAC who underwent PCI-S. We compared patients that received triple antithrombotic therapy (TT) [aspirin, clopidogrel, and coumadin] against other regimes (non-TT) after PCI-S. The primary end point was defined as the occurrence of major bleeding complications that were termed as early major bleeding (EMB) [ 48 h]. Clinical follow-up was performed, and complications were recorded. RESULTS: We studied 104 patients (mean age +/- SD, 72 +/- 8 years; 70% men); TT was used in 51 patients (49%). TT was associated with a higher incidence of LMB (21.6% vs non-TT, 3.8%; p = 0.006) but not of EMB (5.8% vs non-TT, 11.3%; p = 0.33). In multivariate analyses, glycoprotein (GP) IIb/IIIa inhibitor use (hazard ratio [HR], 13.5; 95% confidence interval [CI], 1.7 to 108.3; p = 0.014) and PCI-S of three vessels or left main artery disease (HR, 7.9; 95% CI, 1.6 to 39.2; p = 0.01) were independent predictors for EMB. TT use (HR, 7.1; 95% CI, 1.5 to 32.4; p = 0.012), the occurrence of EMB (HR, 6.7; 95% CI, 1.8 to 25.3; p = 0.005), and baseline anemia (HR, 3.8; 95% CI, 1.2 to 12.5; p = 0.027) were independent predictors for LMB. No differences in major cardiovascular events were observed in patients treated with TT vs non-TT (25.5% vs 21.0%; p = 0.53). CONCLUSION: A high rate of major bleeding is observed in AF patients with indication for OAC undergoing PCI-S who receive TT. GP IIb/IIIa inhibitor use and multivessel/left main artery disease during PCI-S were independent predictors for EMB, while TT use, occurrence of EMB, and baseline anemia were independent predictors for LMB.     

Higher extracellular water to total body water ratio was associated with chronic kidney disease progression in type 2 diabetes

AimWe studied the association between extracellular volume status and chronic kidney disease (CKD) progression; and the role of extracellular volume excess as a potential mediator in the relationship between matrix metalloproteinases (MMP)-2 and CKD progression in Type 2 diabetes mellitus (T2DM).MethodsWe conducted a prospective cohort study of 1079 T2DM patients. Bioelectrical impedance analysis (BIA) was performed to assess body fluid status.ResultsAfter up to 8.6 years of follow-up, 471 (43.7%) patients experienced CKD progression. In the fully adjusted model, extracellular water (ECW)/ total body water (TBW)ratios 0.39–0.40 and > 0.40 were associated with 45% and 78% higher risk of CKD progression respectively. Patients with an increase in ECW/TBW ratio had 40% higher risk of CKD progression compared to those with no change or reduction of ECW/TBW ratio. Higher ECW/TBW ratio accounted for 17.4% of the relationship between MMP-2 and CKD progression in T2DM (p = 0.026).ConclusionsExtracellular volume excess was independently associated with CKD progression in T2DM. Higher ECW/TBW ratio mediated the positive association between MMP-2 and CKD progression. Further studies are needed to elucidate the role of extracellular volume excess in deterioration of renal function.     

Comparison of methods to estimate body fat in growth hormone deficient adults

OBJECTIVE  All of the presently used methods for in-vivo determination of body composition have inherent methodological errors and depend on various assumptions. We have therefore compared several different methods used to measure body fat in adult GH deficiency during GH treatment.
DESIGN  Comparison of body composition data from a two-phase trial with an initial placebo-controlled, double-blind 6-month period, followed by open treatment with GH until all patients had received GH for 12 months.
PATIENTS  Twenty-five patients with known GH deficiency entered the study. Baseline examinations were complete in 23 patients, and 22 patients (16 males, 6 females) completed all examinations after treatment.
MEASUREMENTS  Body fat calculated from total body potassium (TBK) by whole-body ⁴⁰K counting, total body water (TBW) by tritium dilution, total body nitrogen (TBN) by neutron activation, and bioelectric impedance (BIA) measurements were compared to body fat determinations by dual-energy X-ray absorptiometry (DEXA) in two-compartment and multicompartment body composition models.
RESULTS  At baseline, DEXA fat mass agreed well at group level with measurements based on TBW or TBK alone, in a four-compartment model based on TBK and TBW, and a multicompartment model based on bone mineral (by DEXA), TBN and TBW. Body fat by BIA agreed less well. After 12 months of GH treatment, body fat decreased by all methods used. This decrease was smaller by DEXA than by the other methods. The four-compartment model based on TBK and TBW, and TBW alone, showed the best agreement with changes in DEXA fat.
CONCLUSION  All methods showed a decrease of body fat with GH treatment, but variation between methods was considerable.     

Total body water/fat-free mass ratio as a valuable predictive parameter for mortality in maintenance hemodialysis patients

Hydration of fat-free mass (FFM), defined as the ratio of total body water (TBW) to FFM (TBW/FFM), is stable at 0.739 in adult mammals. However, an increase in the TBW/FFM ratio is common in hemodialysis (HD) patients. This study aimed to evaluate the determinants of TBW/FFM and investigate its predictive value for the prognosis of all-cause mortality in HD patients.We enrolled patients undergoing maintenance HD between July 2020 and May 2021. All patients were prospectively followed until death, HD dropout, or until the end of the study (November 1, 2021). A forward stepwise multivariable linear regression analyses was performed to test the independent relationship between TBW/FMM and other clinical variables. Receiver operating characteristic (ROC) analysis was used to discriminate the TBW/FFM with respect to 180-day mortality.Of the 106 patients, 42 had elevated TBW/FFM levels. Multiple linear regression analysis revealed that the TBW/FFM ratio was significantly associated with extracellular water (ECW)/TBW (standardized regression coefficient [β = 1.131, P < .001], phase angle (PhA) [β = 0.453, P < .001], and sex (β = 0.440, P < .001). We calculated the ROC curve (AUC) of TBW/FFM, ECW, ECW/TBW, and intracellular water (ICW) to compare the discriminatory capacities of these parameters in predicting 180-day mortality. The AUC for TBW/FFM (AUC = 0.849; 95% CI, 0.745–0.953) exhibited better discriminatory potential than ECW (AUC = 0.562; 0.410–0.714), although it had a similar predictive potential as the ECW/TBW ratio (AUC = 0.831; 0.731–0.932). High TBW/FFM can be used as a valuable prognostic index for predicting all-cause mortality in patients on HD.     

Measurement of body fat and hydration of the fat-free body in health and disease

Body fat mass, fat-free body mass and body water are basic components of body composition which are used in nutritional and metabolic studies and in patient care. A method of measuring total body fat (TBF), fat-free mass (FFM) and its hydration (TBW/FFM) involving prompt gamma in vivo neutron activation analysis (IVNAA) and tritium dilution has been compared with the more traditional methods of densitometry and skinfold anthropometry in 36 normal volunteers, and with skinfold anthropometry in 56 patients presenting for nutritional support. While the mean values of TBF were in reasonable agreement for the three methods in normals it was founds that skinfold anthropometry underestimated TBF relative to the IVNAA/tritium method by, on average, 3.0 kg (19%) in patients. Furthermore, the ranges of values in normals of the ratio TBW/FFM for the anthropometric (0.62 to 0.80) and densitometric (0.65 to 0.80) methods were much wider than the range for the IVNAA/tritium method (0.69 to 0.76), in which TBW was measured by tritium dilution in all cases. In the patients, the ranges of this ratio were 0.52 to 0.90 for the anthropometric method and 0.67 to 0.82 for the IVNAA/tritium method; clearly anthropometry yields values of TBW/FFM which are outside accepted biological limits. On the basis of these findings, ranges of TBW/FFM are suggested for both normal adults (0.69 to 0.75) and patients requiring nutritional support (0.67 to 0.83). Finally it is concluded that the IVNAA/tritium method is a suitable method for measuring TBF and FFM and particularly so when body composition is abnormal.     

Maternal cardiac systolic function and total body water estimation in normal and gestational hypertensive women

We assessed total body water (TBW) content and cardiac function in 25 normotensive (N) and 22 gestational hypertensive (GH) women matched for age, gestational age, and prepregnancy body mass index (BMI) during the third trimester of gestation. Patients underwent maternal echocardiography, bioelectrical impedance analysis (BIA), and hematocrit (Hct %) evaluation. The TBW:Hct ratio (water balance index, WBI) was calculated. Hct was significantly lower in N vs. GH women (31.9+/-2.2% vs. 36.2+/-2.5; p<0.001). There was no difference in TBW between the two groups. WBI was higher in N vs. GH women (1.35+/-0.20 l.kg(-1) x m(-2) vs. 1.19+/-0.18; p<0.001). N subjects showed a higher stroke volume than GH patients (78.0+/-9.7 ml vs. 67.9+/-10.2; p=0.001). Atrial function was higher in N vs. GH women (left atrial fractional area change 57.4+/-5.1% vs. 42.5+/-7.5; p<0.001). A correlation was found between stroke volume and WBI ( r=0.93, p<0.0001). Maternal cardiac function and WBI are strongly related and might help in understanding the mechanisms of adaptation in normal and hypertensive pregnancy.     

Bioelectrical impedance analysis and other hydration parameters as risk factors for delirium in rural nursing home residents

BACKGROUND: The study investigators conducted a vigorous screening protocol for delirium in rural long-term care (LTC) facilities for a period of 28 days focusing on Bioelectrical Impedance Analysis (BIA) and other hydration parameters as risk factors. METHODS: A two-stage cluster sampling procedure was used to randomly select participants (n = 313) from 13 LTC facilities located in southeastern Iowa, stratified on facility bed size. BIA was used to estimate intracellular water (ICW), extracellular water (ECW), and total body water (TBW) on four occasions--baseline and follow-up days 7, 14, and 28. Volume estimates were calculated as a percent of body weight (%WT). Serum electrolytes and hematology were also measured. Delirium was measured with four strict criteria: a NEECHAM Confusion Scale score < 25, Vigilance "A" score > 2, a Mini-Mental Status Examination < baseline, and a positive Confusion Assessment Method score. RESULTS: There were n = 69 delirium cases (22.0%). Blood urea nitrogen/creatinine ratios greater than 21:1 (odds ratio = 1.76, 95% confidence interval 1.02-3.06). No significant risk for delirium was associated with ICW, ECW, or TBW as a percent of body weight. CONCLUSIONS: Some changes were observed with a slight decrease in ICW between day 7 and day 14 of follow-up that tended to follow an increase in delirium events, but in general the BIA measures did not predict delirium events.     

Impact of intradialytic blood pressure changes on cardiovascular outcomes is independent of the volume status of maintenance hemodialysis patients

Intradialytic systolic blood pressure (SBP) changes are related to the volume status; however, whether SBP change impacts on adverse outcomes depends on the volume status remains uncertain. We retrospectively investigated the relationship among intradialytic changes in SBP, cardiovascular outcomes, and volume status in maintenance hemodialysis patients. We determined SBP changes (ΔSBP) as postdialysis SBP minus predialysis SBP and volume status as the ratio of extracellular water to total body water (ECW/TBW) using bioelectrical impedance analysis. There were 82 (60.3%) with ΔSBP ?20 to 10 mm Hg, 21 (15.4%) with ΔSBP ≤ ?20 mm Hg, and 33 (24.3%) with ΔSBP ≥ 10 mm Hg, and they were followed up for a median of 34 months. Cardiovascular events more frequently occurred in the patients with ΔSBP ≤ ?20 mm Hg and ≥ 10 mm Hg (hazard ratio: 2.3 and 3.0; P = .062 and .006); these associations persisted even after adjusting for postdialysis ECW/TBW (P = .056 and .028). Moreover, ΔSBP ≥ 10 mm Hg was associated with increased cardiovascular mortalities independent of postdialysis ECW/TBW (P = .043). There was an independent association of volume status between considerable SBP decrease or increase during hemodialysis and adverse cardiovascular outcomes. Besides appropriate volume control, other factors related to BP changes during hemodialysis must be investigated.     

Body composition in prepubertal girls: comparison of six methods

OBJECTIVE: To compare estimates of fat mass (FM), fat-free mass (FFM) and percentage body fat (%fat) by six different methods in prepubertal girls. DESIGN: Cross-sectional study. SUBJECTS: Normal-weight, multi-ethnic, prepubertal girls (age=8.5+/-0.4 y, n=101). MEASUREMENTS: Body composition was measured in each child by anthropometry (skinfold thickness using Slaughter equation), dual-energy X-ray absorptiometry (DXA), total body potassium (TBK), isotope dilution for total body water measurement (TBW), multifrequency bioelectrical impedance spectroscopy (BIS), and total body electrical conductivity (TOBEC). RESULTS: TOBEC and skinfold thickness yielded the lowest values of FM followed by DXA, TBK, TBW and BIS, with BIS giving the highest value of FM. All methods were significantly different for FFM, FM and %fat (P<0.001), except FFM by DXA and TBK. The Bland-Altman limits of agreement among the methods reveal that they are not directly interchangeable for FM, FFM, or %fat. The largest mean difference for FM was between TOBEC and BIS (-2.90 kg), whereas the smallest mean difference was between TOBEC and skinfold thickness (-0.14 kg). For FFM, the largest mean difference was also between TOBEC and BIS (2.83 kg), but the smallest mean difference for FFM was between DXA and TBK (-0.03 kg). For %fat, the mean differences were larger, -10.5% for TOBEC and BIS and+9.7% for skinfold thickness and BIS. The closest two techniques for %fat were TOBEC and skinfold thickness (mean difference of -0.62%) and DXA and TBK (-1.81%). CONCLUSIONS: We found that estimates of body composition in prepubertal 8-y-old girls are highly method-dependent and that the six methods studied (DXA, TBK, TBW, TOBEC, BIS and anthropometry) are not directly interchangeable.     

The prediction of total body water from body impedance in young obese subjects.

Almost all formulae for the prediction of total body water (TBW) from body impedance are based on the assumption of a constant conductor configuration--i.e. a constant subject section. In this paper we report on data obtained for a group of 19 young obese subjects (relative weight greater than 120%) and 10 young normal subjects (relative weight 80-110%). In obese subjects, the application of two different formulae generated from normal children gave biased results and led to an underestimation of TBW with respect to the reference value obtained by deuterium oxide dilution. Body mass index accounted for more than 40% of the inter-individual variability, suggesting that body size was not taken sufficiently into consideration by the predictive formulae used. We have used the body surface area as the anthropometrical parameter for the prediction of TBW from body impedance. The regression formula that we propose (TBW = 1.156 x (surface area/body impedance) - 2.356; R = 0.96), although requiring further validation on external populations, seems to provide a more realistic assessment of TBW in young obese subjects. We therefore suggest that the assessment of TBW in young obese subjects requires specifically designed prediction formulae.     

Nutritional Status and Body Fluid Distribution in Chronic Alcoholics Compared With Controls

BACKGROUND: At present few data are available on the total body water (TBW) content and in particular on the distribution of water in the intra- and extracellular compartments (ICW and ECW) of alcoholics. The aim of this study was to evaluate TBW, ICW, and ECW in chronic alcoholic patients. METHODS: Thirty-six alcoholics meeting DSM-III-R criteria for diagnosis (20 men, 16 women; body mass index [BMI] 22.3+/-2.57 kg/m2) were enrolled. Fifty-four healthy social drinkers (31 men, 23 women; BMI 23.7+/-1.68 kg/m2) matched for age and height were used as controls. Systolic and diastolic blood pressure was measured for all cases. All patients were assessed using specific anthropometric measurements. The waist-to-hip ratio (WHR) was used as an indicator of body fat distribution. TBW was measured by isotopic dilution by giving 100 microCi of tritiated water. ICW and ECW were assessed by multifrequence bioelectric impedance analysis (BIA). Basal metabolic rate (BMR) was measured by indirect calorimetry. RESULTS: Body weight was lower in the alcoholics than in the controls (61.9+/-5.5 kg vs. 65.8+/-5.2 kg;p < 0.01), essentially due to a reduction in fat mass. Significantly higher WHR values were found in both male (p < 0.001) and female (p < 0.001) alcoholics than in healthy subjects. A higher ECW/TBW ratio was found in the alcoholics compared with the controls, both as a whole (0.53+/-0.04 vs. 0.41+/-0.03; p < 0.0001) and separated by gender (p < 0.001). CONCLUSIONS: The increased ECW could derive from an increase in cellular permeability related to endothelial damage linked to the vasoconstriction present in the alcoholics and/or to a direct toxic effect of ethanol on cellular membranes. In addition, because the high ECW volumes correlated positively with WHR in the alcoholics, a potential association of these two factors in determining an increased risk of liver disease, hypertension, and cardiovascular disease may exist. Finally, the lower TBW characteristic of women may be one of the reasons for the observed greater rate of toxic effects of ethanol that occur in women.     

A Phase II trial of weekly bortezomib and dexamethasone in veterans with newly diagnosed multiple myeloma not eligible for or who deferred autologous stem cell transplantation

Once‐weekly administration of bortezomib has reduced bortezomib‐induced peripheral neuropathy without affecting response rates, but this has only been demonstrated prospectively in three‐ and four‐ drug combinations. We report a phase II trial of alternate dosing and schedule of bortezomib and dexamethasone in newly diagnosed multiple myeloma patients who are not eligible for or refused autologous stem cell transplantation. Bortezomib 1·6 mg/m² intravenously was given once‐weekly for six cycles, together with dexamethasone 40 mg on the day of and day after bortezomib. Fifty patients were enrolled; 58% did not require any dose modification. The majority of patients had multiple co‐morbidities, including cardiovascular (76%) and renal insufficiency (54%), and the median number of medications prior to enrollment was 13. Of all evaluable patients, the overall response rate was 79% and at least 45% had at least a very good partial response. The median time to first response was 1·3 months (range, 0·25–2·4 months). The progression‐free and overall survivals were 8 months and 46·5 months, respectively. Twenty‐four percent developed worsening neuropathy. We conclude that alternate dosing and scheduling of bortezomib and dexamethasone is both safe and effective for management of newly diagnosed multiple myeloma in frail patients. (ClinicalTrials.gov number, NCT01090921).     

Low serum concentrations of anti-tuberculosis drugs and determinants of their serum levels.

SETTING: Low serum concentrations of anti-tuberculosis drugs have occasionally been associated with treatment failure. OBJECTIVE: To determine the prevalence of low serum concentrations of anti-tuberculosis drugs and to identify the determinants of drug concentrations. DESIGN: Venous blood was obtained 2 h after drug ingestion, and serum levels of isoniazid (INH), rifampicin (RMP), ethambutol (EMB), pyrazinamide (PZA), acetyl INH and 25-desacetyl RMP were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Patients with human immunodeficiency virus co-infection and gastrointestinal disease or diarrhoea were excluded. RESULTS: Among 69 enrolled TB patients, the prevalence of a low 2 h serum concentration of at least one anti-tuberculosis drug was 46.4%. Prevalences of a low concentration of INH, RMP, EMB or PZA were 15.2%, 23.5%, 22.4% and 4.5%, respectively. By multivariate linear regression analysis, the serum concentrations of INH, RMP and PZA were positively associated with dose per kg of body weight (P < 0.05). Moreover, INH concentration was associated with acetyl INH/INH ratio (beta = -8.588, P < 0.001) and EMB concentration was associated with calculated creatinine clearance (beta = -0.025, P < 0.001). CONCLUSION: Low concentrations of anti-tuberculosis drugs are common, and although the clinical significance of low concentrations remains uncertain, it may be necessary to optimise drug doses by therapeutic drug monitoring, especially in patients with an inadequate clinical response to chemotherapy.