Estimated dietary sodium intake in peritoneal dialysis patients using food frequency questionnaires and total urinary and peritoneal sodium losses and assessment of extracellular volumes.

BACKGROUND: Peritoneal dialysis (PD) patients are advised to restrict sodium intake. For best use of resources, rapid screening tools are required for dietary assessments to allow for targeting of patients. We wished to evaluate the usefulness of food frequency questionnaires (FFQ) for estimating dietary sodium. METHODS: Sodium intake was estimated using the Derby Salt Questionnaire (DSQ), and Royal Free Sodium Questionnaire (RFSQ). Body composition was determined by bioimpedance. RESULTS: 90 peritoneal dialysis patients, 52 men (57.8%), mean age 62 ± 15.8 years, were asked to complete the DSQ and RFSQ questionnaires. 88 completed one or more questionnaire, with 87 completing the DSQ and 86 the RFSQ. The median estimated dietary sodium intake 104 (72-145) mmol/day (2.39 (1.64-3.34) g sodium/day) DSQ, and 92 (60-114) mmol/day (2.11 (1.38-2.62) g sodium/day) RFSQ. Younger patients, aged ≤52 years had greater dietary sodium intake compared to those ≥76 years (RFSQ 105.4 (73-129) vs 96 (71-116) mmol/day), p < 0.05. Extracellular water to total body water (ECW/TBW) was greater in those with higher DSQ estimated dietary sodium intake (0.40 ± 0.01 vs 0.39 ± 0.01, p < 0.05). A multivariable model showed that increased dietary sodium intake was independently associated with increased SMM (DSQ odds ratio (OR) 1.17 (95% confidence limits 1.05-1.32, RFSQ OR 1.15 (1.04-1.27, p < 0.05) and raised ECW/TBW (DSQ OR 1.88 (1.22-2.92) p = 0.004, and ECW/height (RFSQ OR 1.42 (1.02-1.98) p = 0.04. CONCLUSIONS: Both questionnaires were acceptable to patients, and the majority were found to be consuming more dietary sodium than recommended. Dietary sodium estimation was associated with SMM and increased ECW.

Improving the spectral resolution and spectral fitting of (1) H MRSI data from human calf muscle by the SPREAD technique.

Proton magnetic resonance spectroscopic imaging ((1) H MRSI) has been used for the in vivo measurement of intramyocellular lipids (IMCLs) in human calf muscle for almost two decades, but the low spectral resolution between extramyocellular lipids (EMCLs) and IMCLs, partially caused by the magnetic field inhomogeneity, has hindered the accuracy of spectral fitting. The purpose of this paper was to enhance the spectral resolution of (1) H MRSI data from human calf muscle using the SPREAD (spectral resolution amelioration by deconvolution) technique and to assess the influence of improved spectral resolution on the accuracy of spectral fitting and on in vivo measurement of IMCLs. We acquired MRI and (1) H MRSI data from calf muscles of three healthy volunteers. We reconstructed spectral lineshapes of the (1) H MRSI data based on field maps and used the lineshapes to deconvolve the measured MRS spectra, thereby eliminating the line broadening caused by field inhomogeneities and improving the spectral resolution of the (1) H MRSI data. We employed Monte Carlo (MC) simulations with 200 noise realizations to measure the variations of spectral fitting parameters and used an F-test to evaluate the significance of the differences of the variations between the spectra before SPREAD and after SPREAD. We also used Cramer-Rao lower bounds (CRLBs) to assess the improvements of spectral fitting after SPREAD. The use of SPREAD enhanced the separation between EMCL and IMCL peaks in (1) H MRSI spectra from human calf muscle. MC simulations and F-tests showed that the use of SPREAD significantly reduced the standard deviations of the estimated IMCL peak areas (p < 10(-8) ), and the CRLBs were strongly reduced (by ~37%).

Assessment of fluid and nutritional status using multifrequency bioelectrical impedance analysis in peritoneal dialysis patients.

BACKGROUND/AIMS: The purpose of this study was to evaluate the clinical usefulness and relevance of bioelectrical impedance analysis (BIA) for assessing the fluid and nutritional status in peritoneal dialysis (PD) patients. METHODS: Statistical analyses between various measures of fluid and nutritional status were performed in 106 cases of 64 patients. RESULTS: Extracellular fluid/total body water (ECF/TBW) was correlated with systolic blood pressure, extremity edema, and antihypertensive medications (p = 0.042, p < 0.001, and p = 0.029, respectively). Body cell mass (BCM)/height(2) was correlated with SGA rating and PCR (p < 0.001 and p = 0.002, respectively). ECF/TBW and BCM/height(2) significantly predicted extremity edema (p < 0.001) and SGA rating (p = 0.001), respectively. ROC analysis yielded an ECF/TBW cut-off of 0.36 and a BCM/height(2) cut-off of 11.23. When the BCM/height(2) cut-off of 11.23 was applied to subclinical patients (SGA score ≥6), a significant difference in SGA rating was detected in subgroups (p = 0.010). CONCLUSION: BIA yields useful and relevant information about hydration and nutritional status in PD patients.

Metronidazole and hydroxymetronidazole central nervous system distribution: 1. microdialysis assessment of brain extracellular fluid concentrations in patients with acute brain injury.

The distribution of metronidazole in the central nervous system has only been described based on cerebrospinal fluid data. However, extracellular fluid (ECF) concentrations may better predict its antimicrobial effect and/or side effects. We sought to explore by microdialysis brain ECF metronidazole distribution in patients with acute brain injury. Four brain-injured patients monitored by cerebral microdialysis received 500 mg of metronidazole over 0.5 h every 8 h. Brain dialysates and blood samples were collected at steady state over 8 h. Probe recoveries were evaluated by in vivo retrodialysis in each patient for metronidazole. Metronidazole and OH-metronidazole were assayed by high-pressure liquid chromatography, and a noncompartmental pharmacokinetic analysis was performed. Probe recovery was equal to 78.8% ± 1.3% for metronidazole in patients. Unbound brain metronidazole concentration-time curves were delayed compared to unbound plasma concentration-time curves but with a mean metronidazole unbound brain/plasma AUC0-τ ratio equal to 102% ± 19% (ranging from 87 to 124%). The unbound plasma concentration-time profiles for OH-metronidazole were flat, with mean average steady-state concentrations equal to 4.0 ± 0.7 µg ml(-1). This microdialysis study describes the steady-state brain distribution of metronidazole in patients and confirms its extensive distribution.

Assessment of buffer systems for harvesting proteins from tissue interstitial fluid for proteomic analysis.

Tissue interstitial fluid (TIF) bathes cells in tissues, and it is hypothesized that TIF proximal to a developing tumor may contain an enriched population of tumor-specific shed and secreted proteins relative to peripheral blood. Extraction of TIF proteins is typically accomplished through passive incubation of surgically resected tissues in phosphate buffered saline (PBS); however, its influence on cellular activity and viability has not been fully explored. The present investigation sought to characterize whether different buffer systems influence the recovered TIF proteome. Five TIF buffer systems were investigated including PBS, Dulbecco's modified Eagle medium (DMEM), and three organ transplantation preservative solutions: Celsior solution S (CS), histidine-tryptophan-ketoglutarate (HTK), and University of Wisconsin (UW). Kidney tumor, adjacent normal kidney, and ovarian tumor tissues were incubated in each of the buffer systems, and the harvested TIF proteins were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Although the present results indicate that no significant differences exist in the recovered proteins from these two neoplasms between the five solution groups, additional sample preparative steps are required prior to LC-MS/MS for TIF proteins harvested from DMEM, UW, CS, and HTK. These data support that PBS is a suitable and convenient solution for harvesting TIF proteins for MS-based proteomics.

Utility of osteopontin and serum mesothelin in malignant pleural mesothelioma diagnosis and prognosis assessment.

PURPOSE: Malignant mesothelioma is a highly aggressive tumor and is often diagnosed too late for a curative treatment. We compared diagnostic and prognostic values of mesothelin and osteopontin in 172 patients suspected of malignant pleural mesothelioma (MPM) and in a control group of 112 asymptomatic asbestos-exposed subjects. EXPERIMENTAL DESIGN: Osteopontin and mesothelin were assayed with commercial ELISA kits in a series of 43 patients with pleural metastases of various carcinomas, 33 patients with benign pleural lesions associated with asbestos exposure, 96 patients with MPMs, and 112 asbestos-exposed healthy subjects. Results were correlated with patient's diagnosis and survival. RESULTS: Serum osteopontin level was higher in MPM patients compared with healthy asbestos-exposed subjects and had a good capability to distinguish between these two populations. However, osteopontin was unable to distinguish between MPM and pleural metastatic carcinoma or benign pleural lesions associated with asbestos exposure. Neither plasma nor pleural fluid osteopontin were more powerful in this respect. Serum mesothelin had a good ability for diagnosing MPM but was unable to identify patients with nonepithelioid mesothelioma subtypes. Survival analysis identified tumor histologic subtype along with serum osteopontin and serum mesothelin as independent prognostic factors in mesothelioma patients. CONCLUSIONS: Osteopontin has a lower diagnostic accuracy than mesothelin in patients suspected of MPM. Insufficient specificity limits osteopontin utility as diagnostic marker. Both molecules have a potential value as prognostic markers.

Assessment of trueness of a glucose monitor using interstitial fluid and whole blood as specimen matrix.

BACKGROUND: Interstitial fluid (ISF) is a specimen of increasing interest for glucose measurements because it can be obtained in a minimally invasive manner. Our previous study showed that sufficient ISF can be obtained using microneedles to measure glucose with a conventional electrochemical glucose monitor. The aim of this study was to assess the trueness of this glucose monitor using split-sample comparison with whole blood. We used ISF as specimen and our gas chromatography/mass spectrometry (GC/MS) method as reference. METHODS: We obtained 50 ISF samples and 40 whole blood samples from hairless Sprague- Dawley rats and analyzed for glucose by both methods. RESULTS: For whole blood, a non-significant bias of 5.7% (+/-2 SD: -54.9% to 66.3%) was determined. ISF glucose measurements showed a significant constant bias of 29.5% (+/-2 SD: -85.0% to 144%), which seems to be caused in part by the lack of red blood cells in ISF. The correlation coefficients were 0.782 and 0.679 for whole blood and ISF, respectively. CONCLUSIONS: The assessed electrochemical glucose monitor shows a close agreement with our GC/MS reference method for whole blood, for which this monitor was optimized. When glucose measurements are performed with ISF as matrix, the observed bias needs to be taken into consideration. Further studies are necessary to elucidate the reasons for the wide dispersion of data for ISF.

Local inhibition of organic cation transporters increases extracellular serotonin in the medial hypothalamus.

In the rat dorsomedial hypothalamus (DMH), serotonin (5-HT) concentrations are altered rapidly in response to acute stressors. The mechanism for rapid changes in 5-HT concentrations in the DMH is not clear. We hypothesize that the mechanism involves corticosteroid-induced alterations in the uptake of 5-HT from extracellular fluid through the action of corticosterone-sensitive organic cation transporters (OCTs). To determine if OCTs affect the clearance of 5-HT from the extracellular fluid compartment within the medial hypothalamus (MH), the OCT blocker, decynium 22 (0, 10, 30, or 100 microM), was perfused into the MH via a microdialysis probe, and dialysate 5-HT concentrations were measured at 20 min intervals. In addition, home cage behavior was measured both before and after drug administration. Inhibition of OCTs in the MH resulted in a reversible dose-dependent increase in extracellular 5-HT concentration. Increases in extracellular 5-HT concentrations were associated with increases in grooming behavior in rats treated with the highest concentration of decynium 22. No other behavioral responses were observed following administration of any concentration of decynium 22. These findings are consistent with the hypothesis that OCTs in the MH play an important role in the regulation of serotonergic neurotransmission and specific behavioral responses. Because the MH plays an important role in the neuroendocrine, autonomic, and behavioral responses to stress-related stimuli, these data lead to new questions regarding the role of interactions between corticosterone and corticosterone-sensitive OCTs in stress-induced 5-HT accumulation within the MH as well as the physiological and behavioral consequences of these interactions.

Pharmacodynamic assessment of the benztropine analogues AHN-1055 and AHN-2005 using intracerebral microdialysis to evaluate brain dopamine levels and pharmacokinetic/pharmacodynamic modeling.

PURPOSE: The benztropine (BZT) analogues bind with high affinity to the dopamine transporter (DAT) and demonstrate a behavioral and pharmacokinetic profile unlike that of cocaine. The development of a predictive pharmacokinetic/pharmacodynamic (PK/PD) model to characterize the concentration-effect relationship between the BZT analogues and brain dopamine (DA) levels is an important step in the evaluation of these compounds as potential cocaine abuse pharmacotherapies. Hence, the objective of this study was to mathematically characterize the PD of BZT analogues and cocaine, using appropriate PK/PD models. METHODS: Dialysis probes were stereotaxically implanted into the nucleus accumbens of Sprague-Dawley rats (275-300 g). Extracellular fluid (ECF) DA levels were measured after intravenous administration of the BZT analogues AHN-1055 and AHN-2005, as well as cocaine using high performance liquid chromatography-electrochemical detection (HPLC-ECD). PD models were used to describe the relationship between the BZT analogues or cocaine and brain microdialysate DA, and suitability was based on standard goodness-of-fit criteria. RESULTS: The BZT analogues produced a sustained increase in brain microdialysate DA levels in comparison to cocaine. The time of maximum concentration (T(max)) for brain microdialysate DA was 2 h for AHN-1055 and 1 h for AHN-2005 compared to a T(max) of 10 min for cocaine. The duration of brain microdialysate DA elevation was approximately 12-24 h for the BZTs in comparison to 1 h for cocaine. An indirect model with inhibition of loss of response and a sigmoid E(max) model best described the PK/PD for the BZT analogues and cocaine, respectively. The 50% of maximum inhibition (IC(50)) of the loss of DA was lower for AHN-2005 (226 +/- 27.5 ng/ml) compared to AHN-1055 (321 +/- 19.7 ng/ml). In addition, the EC(50) for cocaine was 215 +/- 11.2 ng/ml. CONCLUSIONS: The slow onset and long duration of BZT analogue-induced DA elevation may avoid the reinforcing effects and craving of cocaine. Further, the developed models will be useful in characterizing the PK/PD of other analogues and aid in the assessment of the therapeutic efficacy of the BZT analogues as substitute medications for cocaine abuse.

[UHF-dielectrometry in the assessment of the structural organization of salt solutions and interstitial fluids in normal and cicatricial tissues]. / KVCh-diélektrometriia pri otsenke strukturnoi organizatsii rastvorov solei i tkanevykh zhidkostei zdorovoi i rubtsovoi tkani.

The complex dielectric permittivity of salt solutions with positive and negative salvation as well as healthy and cicatricially changed human skin in situ at the frequencies of 42 and 56.6 GHz was measured. The relation between the dielectric characteristics of water and diluted salt solutions and changes in their structural organization conditioned by different temperatures of samples and the type of salvation of electrolytes was studied. The differences in the dielectric characteristics of healthy and cicatricially changed skin are interpreted in terms of the dependence of the structural organization of interstitial fluids on the morphological and functional state of biological tissues.

Continuous glucose monitoring with glucose sensors: calibration and assessment criteria.

Continuous glucose monitoring (CM) by means of minimally invasive or noninvasive glucose sensors can help to further optimize metabolic control in patients with diabetes without need for frequent capillary blood glucose measurements. Most glucose sensors measure glucose concentration in the interstitial fluid (ISF). Because of the varying conditions in this compartment, a general in vitro calibration ( = factory calibration) by the manufacturer appears not to be possible. Therefore, calibration of the sensor signal must be performed by the patient himself repeatedly. The calibration procedure can be performed by means of conventional capillary blood glucose measurements in order to transform the sensor signals obtained from the specific compartment (e.g., ISF) into "blood" glucose values. A number of aspects can influence the validity of this procedure. The relationship between changes in blood glucose and in ISF glucose, in both time and concentration dimensions, is not well understood, especially during dynamic changes. The physical lag time, which critically depends on the glucose sensor technology used, can also introduce a systematic calibration error. After the first calibration, usually performed some hours after the application of a given glucose sensor, recalibration at certain intervals is necessary. Therefore, patients should critically assess the values displayed by a CM system. In the case of implausible glucose values they should verify the results by means of a conventional capillary glucose measurement. Up to now there is no consensus on assessment criteria to be used for evaluation of CM system performance and calibration quality. Existing methods of displaying CM values against corresponding reference values, including linear regression analysis and error grid analysis, as well as numeric criteria such as System Error, Predicted Error Sum of Squares (in %), and Mean Absolute Deviation are not generally applicable to CM. It appears as if they do not allow sufficient description of data obtained with CM systems. There is a pressing need to develop novel adequate assessment criteria enabling a better characterization of CM system performance. If these were used uniformly by all manufacturers and scientists assessing CM systems, this would allow a fair comparison of the performance of different systems.

Plasma brain natriuretic peptide concentration on assessment of hydration status in hemodialysis patient.

BACKGROUND: Brain natriuretic peptide (BNP) is released into circulation in response to ventricular dilatation and pressure overload. Plasma BNP concentration correlates with left ventricular mass and dysfunction, which is prevalent in hemodialysis (HD) patients. METHODS: To evaluate the potential of BNP level for determination of hydration status, we measured inferior vena caval diameter (IVCD) and BNP levels and performed bioimpedance analysis in 49 HD patients. RESULTS: Pre-HD BNP levels remained unchanged after HD. Agreement between IVCD and pre-HD BNP level in overhydration was significant (kappa = 0.304). The area under the receiver operating characteristic (ROC) curve for overhydration was 0.819 for pre-HD BNP level. When extracellular fluid/total-body water (ECF/TBW) ratios of HD patients were compared with those of 723 controls, pre- and post-HD BNP levels were significantly greater in overhydrated patients. The area under the ROC curve for overhydration by ECF/TBW ratio was 0.781 for pre-HD BNP level. However, there was no significance for pre- or post-HD BNP levels on assessment of normohydration or underhydration. Pre-HD BNP level correlated significantly with post-HD BNP level, post-HD diastolic blood pressure, pulse pressure, and ECF/TBW ratio. IVCD correlated significantly with post-HD BNP level. CONCLUSION: BNP level seems to have a limited potential for assessment of overhydration in HD patients.