Assessment of the size selectivity of peritoneal permeability by the restriction coefficient to protein transport.

Transport of serum proteins from the circulation to peritoneal dialysate in peritoneal dialysis patients mainly focused on total protein. Individual proteins have hardly been studied. We determined serum and effluent concentrations of four individual proteins with a wide molecular weight range routinely in the standardised peritoneal permeability analysis performed yearly in all participating patients. These include ß2-microglobulin, albumin, immunoglobulin G and α2-macroglobulin. The dependency of transport of these proteins on their molecular weight and diffusion coefficient led to the development of the peritoneal protein restriction coefficient (PPRC), which is the slope of the relation between the peritoneal clearances of these proteins and their free diffusion coefficients in water, when plotted on a double logarithmic scale. The higher the PPRC, the more size restriction to transport. In this review, we discuss the results obtained on the PPRC under various conditions, such as effects of various osmotic agents, vasoactive drugs, peritonitis and the hydrostatic pressure gradient. Long-term follow-up of patients shows an increase of the PPRC, the possible causes of which are discussed. Venous vasculopathy of the peritoneal microcirculation is the most likely explanation.

Reproducibility of the peritoneal regression grading score for assessment of response to therapy in peritoneal metastasis.

AIMS: The four-tiered peritoneal regression grading score (PRGS) assesses the response to chemotherapy in peritoneal metastasis (PM). The PRGS is used, for example, to assess the response to pressurised intraperitoneal aerosol chemotherapy (PIPAC). However, the reproducibility of the PRGS is currently unknown. We aimed to evaluate the inter- and intraobserver variability of the PRGS. METHODS AND RESULTS: Thirty-three patients who underwent at least three PIPAC treatments as part of the PIPAC-OPC1 or PIPAC-OPC2 clinical trials at Odense University Hospital, Denmark, were included. Prior to each therapy cycle, peritoneal quadrant biopsies were obtained and three haematoxylin and eosin (H&E)-stained step sections were scanned and uploaded to a pseudonymised web library. For determining interobserver variability, eight pathologists assessed the PRGS for each quadrant biopsy, and Krippendorff's alpha and intraclass correlation coefficients (ICCs) were calculated. For determining intraobserver variability, three pathologists repeated their own assessments and Cohen's kappa and ICCs were calculated. A total of 331 peritoneal biopsies were analysed. Interobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was moderate to good/substantial. The intraobserver variability for PRGS of each biopsy and for the mean and maximum PRGS per biopsy set was good to excellent/almost perfect. CONCLUSIONS: Our data support the PRGS as a reproducible and useful tool to assess response to intraperitoneal chemotherapy in PM. Future studies should evaluate the prognostic and predictive role of the PRGS.

A Large Intraperitoneal Residual Volume Hampers Adequate Volumetric Assessment of Osmotic Conductance to Glucose.

BACKGROUND: In end-stage renal disease patients treated with peritoneal dialysis (PD), the osmotic conductance to glucose (OCG) represents the intrinsic ability of the membrane to transport water in response to a crystalloid osmotic gradient. A progressive loss of OCG in long-term PD patients indicates the development of fibrosis in the peritoneal interstitium, and helps identify patients at risk for encapsulating peritoneal sclerosis. The double mini-peritoneal equilibration test (PET) has been proposed as a simple method to assess OCG using the difference in initial ultrafiltration rates generated by 2 successive dwells using 1.36% and 3.86% glucose-based, 1-h PET. However, the presence of a large peritoneal residual volume (RV) may potentially interfere with the correct evaluation of drained volumes, limiting the reliability of OCG assessed by the double mini-PET. METHODS: We retrospectively reviewed data from 53 peritoneal function tests in 35 consecutive PD patients starting PD at our center between March 2013 and March 2017. The test consisted of a uni-PET (double mini-PET combined with a 3.86%, 4-h PET) performed at PD start, then yearly. In addition to peritoneal solute transport rate and net ultrafiltration, the tests provided information about osmotic water transport (OCG, sodium sieving, and free-water transport) as well as the RV estimated from albumin dilution. RESULTS: Contrary to sodium sieving, net ultrafiltration, and free-water transport, OCG did not correlate with any of the other parameters of osmotic water transport. In multivariate regression analyses, the RV was identified as the only determinant of OCG, while it did not alter the robust association between sodium sieving/free-water transport and their respective determinants. Considering only baseline tests or the whole series of tests, the presence of a large intraperitoneal RV was associated with discrepant values between OCG and sodium sieving, and with an artificial increase in OCG. CONCLUSIONS: A large RV leads to significant overestimation of OCG using the double mini-PET, potentially reducing the ability of OCG to identify patients with progressive fibrosis in the peritoneal interstitium. On the other hand, sieving of the dialysate sodium, a biochemical surrogate for OCG, is independent of the RV and may therefore be more reliable. A call for caution is warranted in patients with a large RV to avoid misinterpretation of OCG values derived from the double mini-PET.

Changes of peritoneal transport parameters with time on dialysis: assessment with sequential peritoneal equilibration test.

BACKGROUND: Sequential peritoneal equilibration test (sPET) is based on the consecutive performance of the peritoneal equilibration test (PET, 4-hour, glucose 2.27%) and the mini-PET (1-hour, glucose 3.86%), and the estimation of peritoneal transport parameters with the 2-pore model. It enables the assessment of the functional transport barrier for fluid and small solutes. The objective of this study was to check whether the estimated model parameters can serve as better and earlier indicators of the changes in the peritoneal transport characteristics than directly measured transport indices that depend on several transport processes. METHODS: 17 patients were examined using sPET twice with the interval of about 8 months (230 ± 60 days). RESULTS: There was no difference between the observational parameters measured in the 2 examinations. The indices for solute transport, but not net UF, were well correlated between the examinations. Among the estimated parameters, a significant decrease between the 2 examinations was found only for hydraulic permeability LpS, and osmotic conductance for glucose, whereas the other parameters remained unchanged. These fluid transport parameters did not correlate with D/P for creatinine, although the decrease in LpS values between the examinations was observed mostly for patients with low D/P for creatinine. CONCLUSIONS: We conclude that changes in fluid transport parameters, hydraulic permeability and osmotic conductance for glucose, as assessed by the pore model, may precede the changes in small solute transport. The systematic assessment of fluid transport status needs specific clinical and mathematical tools beside the standard PET tests.

Is there such a thing as biocompatible peritoneal dialysis fluid?

Introduction of the so-called biocompatible peritoneal dialysis (PD) fluids was based on a large body of experimental evidence and various clinical trials suggesting important clinical benefits. Of these, until now, only preservation of residual renal function-likely due to lower glucose degradation product load and, in case of icodextrin, improved fluid and blood pressure control-have consistently been proven, whereas the impact on important clinical endpoints such as infectious complications, preservation of PD membrane transport function, and patient outcome, are still debated. In view of the high morbidity and mortality rates of PD patients, novel approaches are warranted and comprise the search for alternative osmotic agents and enrichment of PD fluids with specific pharmacologic agents, such as alanyl-glutamine, potentially counteracting local but also systemic sequelae of uremia and PD.

A cost-effective method to get insight into the peritoneal dialysate effluent proteome.

Protein depletion with acetonitrile and protein equalization with dithiothreitol have been assessed with success as proteomics tools for getting insight into the peritoneal dialysate effluent proteome. The methods proposed are cost-effective, fast and easy of handling, and they match the criteria of analytical minimalism: low sample volume and low reagent consumption. Using two-dimensional gel electrophoresis and peptide mass fingerprinting, a total of 72 unique proteins were identified. Acetonitrile depletes de PDE proteome from high-abundance proteins, such as albumin, and enriches the sample in apolipo-like proteins. Dithiothreitol equalizes the PDE proteome by diminishing the levels of albumin and enriching the extract in immunoglobulin-like proteins. The annotation per gene ontology term reveals the same biological paths being affected for patients undergoing peritoneal dialysis, namely that the largest number of proteins lost through peritoneal dialysate are extracellular proteins involved in regulation processes through binding. SIGNIFICANCE: Renal failure is a growing problem worldwide, and particularly in Europe where the population is getting older. Up-to-date there is a focus of interest in peritoneal dialysis (PD), as it provides a better quality of life and autonomy of the patients than other renal replacement therapies such as haemodialysis. However, PD can only be used during a short period of years, as the peritoneum lost its permeability through time. Therefore to make a breakthrough in PD and consequently contribute to better healthcare system it is urgent to find a group of biomarkers of peritoneum degradation. Here we report on two cost-effective methods for protein depletion in peritoneal dialysate effluent (PDE). The use of ACN and DTT over PDE to deplete high abundant proteins or to equalize the concentration of proteins, respectively, performs well and with similar protein profiles than when the same chemicals are used in human plasma samples. ACN depletes de PDE proteome from large proteins, such as albumin, and enriches the sample in apolipoproteins. DTT equalizes the PDE proteome by diminishing the levels of large proteins such as albumin and enriching the extract in immunoglobulins. Although the number and type of proteins identified are different, the annotation per gene ontology term reveals the same biological paths being affected for patients undergoing peritoneal dialysate. Thus, the largest number of proteins lost through peritoneal dialysate belongs to the group of extracellular proteins involved in regulation processes through binding. As for the searching of biomarkers, DTT seems to be the most promising of the two methods because acts as an equalizer and it allows interrogating more proteins in the same sample.

Assessment of asbestos body formation by high resolution FEG-SEM after exposure of Sprague-Dawley rats to chrysotile, crocidolite, or erionite.

This work presents a comparative FEG-SEM study of the morphological and chemical characteristics of both asbestos bodies and fibres found in the tissues of Sprague-Dawley rats subjected to intraperitoneal or intrapleural injection of UICC chrysotile, UICC crocidolite and erionite from Jersey, Nevada (USA), with monitoring up to 3 years after exposure. Due to unequal dosing based on number of fibres per mass for chrysotile with respect to crocidolite and erionite, excessive fibre burden and fibre aggregation during injection that especially for chrysotile would likely not represent what humans would be exposed to, caution must be taken in extrapolating our results based on instillation in experimental animals to human inhalation. Notwithstanding, the results of this study may help to better understand the mechanism of formation of asbestos bodies. For chrysotile and crocidolite, asbestos bodies are systematically formed on long asbestos fibres. The number of coated fibres is only 3.3% in chrysotile inoculated tissues. In UICC crocidolite, Mg, Si, and Fe are associated with the fibres whereas Fe, P and Ca are associated with the coating. Even for crocidolite, most of the observed fibres are uncoated as coated fibres are about 5.7%. Asbestos bodies do not form on erionite fibres. The crystal habit, crystallinity and chemistry of all fibre species do not change with contact time, with the exception of chrysotile which shows signs of leaching of Mg. A model for the formation of asbestos bodies from mineral fibres is postulated. Because the three fibre species show limited signs of dissolution in the tissue, they cannot act as source of elements (primarily Fe, P and Ca) promoting nucleation and growth of asbestos bodies. Hence, the limited number of coated fibres should be due to the lack of nutrients or organic nature.

Peritoneal fluid transport: mechanisms, pathways, methods of assessment.

Fluid removal during peritoneal dialysis is controlled by many mutually dependent factors and therefore its analysis is more complex than that of the removal of small solutes used as markers of dialysis adequacy. Many new tests have been proposed to assess quantitatively different components of fluid transport (transcapillary ultrafiltration, peritoneal absorption, free water, etc.) and to estimate the factors that influence the rate of fluid transport (osmotic conductance). These tests provide detailed information about indices and parameters that describe fluid transport, especially those concerning the problem of the permanent loss of ultrafiltration capacity (ultrafiltration failure). Different theories and respective mathematical models of mechanisms and pathways of fluid transport are presently discussed and applied, and some fluid transport issues are still debated.

Sequential peritoneal equilibration test: a new method for assessment and modelling of peritoneal transport.

BACKGROUND: In spite of many peritoneal tests proposed, there is still a need for a simple and reliable new approach for deriving detailed information about peritoneal membrane characteristics, especially those related to fluid transport. METHODS: The sequential peritoneal equilibration test (sPET) that includes PET (glucose 2.27%, 4 h) followed by miniPET (glucose 3.86%, 1 h) was performed in 27 stable continuous ambulatory peritoneal dialysis patients. Ultrafiltration volumes, glucose absorption, ratio of concentration in dialysis fluid to concentration in plasma (D/P), sodium dip (Dip D/P Sodium), free water fraction (FWF60) and the ultrafiltration passing through small pores at 60 min (UFSP60), were calculated using clinical data. Peritoneal transport parameters were estimated using the three-pore model (3p model) and clinical data. Osmotic conductance for glucose was calculated from the parameters of the model. RESULTS: D/P creatinine correlated with diffusive mass transport parameters for all considered solutes, but not with fluid transport characteristics. Hydraulic permeability (L(p)S) correlated with net ultrafiltration from miniPET, UFSP60, FWF60 and sodium dip. The fraction of ultrasmall pores correlated with FWF60 and sodium dip. CONCLUSIONS: The sequential PET described and interpreted mechanisms of ultrafiltration and solute transport. Fluid transport parameters from the 3p model were independent of the PET D/P creatinine, but correlated with fluid transport characteristics from PET and miniPET.

Semiquantitative assessment of the microdistribution of fluorescence-labeled monoclonal antibody in small peritoneal disseminations of ovarian cancer.

Uniform antibody microdistribution throughout tumor nodules is crucial for antibody-targeted therapy, because non-uniform microdistribution leads to suboptimal therapeutic effect, a commonly observed limitation of therapeutic antibodies. Herein, we evaluated the microdistribution of different doses of intraperitoneally injected fluorescence-labeled full-antibody trastuzumab (15, 50, and 150 microg) and its Fab fragment (trastuzumab-Fab: 15 and 50 microg) in a mouse model of ovarian cancer with peritoneal disseminated tumor. A semiquantitative approach (central/peripheral accumulation ratio; C/P ratio) was developed using in situ fluorescence microscopy. Furthermore, we compared the microdistribution of intact trastuzumab with a mixed injection of trastuzumab and trastuzumab-Fab or serial injections of trastuzumab using in situ multicolor fluorescence microscopy. Fluorescence images after the administration of 15 or 50 microg trastuzumab and 15 microg trastuzumab-Fab demonstrated antibody accumulation in the tumor periphery, whereas administration of 150 microg trastuzumab and 50 microg trastuzumab-Fab showed relatively uniform accumulation throughout the tumor nodule. Using serial injections (19-h interval) of trastuzumab-rhodamine green and carboxytetramethylrhodamine (TAMRA), it was observed that the latterly injected trastuzumab-TAMRA was distributed more centrally than trastuzumab-rhodamine green injected first, whereas no difference was observed in the control mixed-injection group. Moreover, the mixed injection of trastuzumab and trastuzumab-Fab showed that trastuzumab-Fab distributed more centrally than the same amount of co-injected trastuzumab. Our results suggest that the strategies of increasing dose and using Fab fragments can be used to achieve a uniform antibody distribution within peritoneal disseminated nodules after intraperitoneal injection. Furthermore, serial-injection and mixed-injection strategies can modify antibody microdistribution within tumors and have the potential for preferential delivery of anticancer drugs to either the tumor periphery or its center.

Peritoneal vascular density assessment using narrow-band imaging and vascular analysis software, and cytokine analysis in women with and without endometriosis.

The development and onset of endometriosis is associated with angiogenesis and angiogenic factors including cytokines. We analyzed intrapelvic conditions in women with endometriosis via vascular density assessment of grossly normal peritoneum and determination of cytokine levels in peritoneal fluid. Seventy-three patients underwent laparoscopic surgery because of gynecologic disease including endometriosis in our department using a narrow-band imaging system. Each patient was analyzed for peritoneal vascular density using commercially available vascular analysis software (SolemioENDO ProStudy; Olympus Corp, Tokyo, Japan). Each patient was also subjected to analysis of interleukin 6 (IL-6), IL-8, tumor necrosis factor-alpha, and vascular endothelial growth factor concentrations in peritoneal fluid. We defined 4 groups as follows: group 1, endometriosis: gonadotropin-releasing hormone (GnRH) agonist administration group (n=27); group 2, endometriosis: GnRH agonist nonadministration group (n=15); group 3, no endometriosis: GnRH agonist administration group (n=18); and group 4, no endometriosis: GnRH agonist nonadministration group (n=13). No significant differences in peritoneal vascular density between the 4 groups were found under conventional light; however, under narrow-band light, vascular density in the endometriosis groups (groups 1 and 2) was significantly higher. Cytokine analysis of the 4 groups determined that IL-6 and IL-8 concentrations were significantly higher compared with the no endometriosis groups (groups 3 and 4). Tumor necrosis factor-alpha and vascular endothelial growth factor concentrations were not significantly different between groups. In endometriosis, peritoneal vascular density was significantly higher as assessed using the narrow-band imaging system and SolemioENDO ProStudy, whereas GnRH agonist did not obviously decrease vascular density but IL-6 concentration was lower in the GnRH agonist administration group.

Does the biocompatibility of the peritoneal dialysis solution matter in assessment of peritoneal function?

BACKGROUND: Peritoneal function tests are performed in peritoneal dialysis (PD) patients to characterize peritoneal membrane status. A low pH/high glucose degradation product (GDP) dialysis solution is used as the test solution. The objective of the present study was to compare a 3.86% glucose, low pH/high GDP dialysis solution (pH 5.5) with a 3.86% glucose, normal pH/low GDP dialysis solution (pH 7.4) in assessments of peritoneal membrane function. METHODS: Two standard peritoneal permeability analyses (SPA) were performed in 10 stable PD patients within 2 weeks. One SPA was done with the 3.86% low pH/high GDP solution, and the other with the 3.86% normal pH/low GDP solution. The sequence of the two tests was randomized. RESULTS: Fluid transport parameters and glucose absorption were not different between the two groups. No differences were found for the mass transfer area coefficients (MTACs) of low molecular weight solutes calculated over the whole dwell. However, MTAC urea in the first hour of the dwell was higher in the test done with low pH/high GDP dialysate, suggesting more peritoneal vasodilation. No difference was found in protein clearances. Sodium sieving at multiple time points during the dwell was similar with the two solutions. CONCLUSION: The results obtained with the glucose-containing normal pH/low GDP dialysis solution were similar to those obtained with the glucose-containing low pH/high GDP dialysate in assessments of peritoneal membrane function.

Clinical effects of combined therapy with peritoneal dialysis and hemodialysis.

The fundamental objective of dialysis is to maintain the dose of solute clearance and ultrafiltration (UF). When peritoneal dialysis (PD) patients cannot maintain target clearances, the dialysis dose needs to be increased. The means of increasing dose by PD alone are limited, especially in patients with UF failure. Combination therapy with PD and hemodialysis (PD+HD) is the simplest way to solve this problem. The general prescription for PD+HD should be 5-6 days of PD and 1 session of HD weekly. To determine the adequacy of PD+HD, we adopted the equivalent renal clearance (EKR), transforming the weekly Kt/V from PD and then evaluating the total clearance from both modalities. The weekly PD+HD regimen improves clinical status in patients in whom PD alone does not result in dialysis adequacy, and it permits a substantial prolongation of PD. The complementary effects of PD and HD improve clinical status and prognosis in patients undergoing dialysis; we therefore propose to use the term "complementary dialysis" for this technique.

[Extended assessment of peritoneal transport kinetics of substances and water as an important element of integrated dialysis care]. / Rozszerzona ocena kinetyki transportu przezotrzewnowego czqsteczek i wody jako wazny element koncepcji zintegrowanej opieki dializacyjnej.

UNLABELLED: The concept of integrated dialysis care is based on the choice of the most optimal method of renal replacement therapy for particular patient in particular period of disease. In many cases peritoneal dialysis (PD) is the initial therapy. PD modalities and regimens are modified according to values of parameters of ultrafiltration and adequacy. The routinely used methods of analysis of peritoneal transport are very useful for general assessment of properties of peritoneum as a dialysis membrane. However, the application of these methods do not guarantee the full assessment of peritoneal transport kinetics of water and substances. Therefore, the capabilities of the most adequate modification are limited. The tests based on mathematical models taking into account the kinetics of intraperitoneal dialysate volume seem to be the right supplement of standard methods. MATERIALS AND METHODS: To illustrate the problem mentioned above, the aim of this study was comparison of peritoneal transport of substances and water in two groups of patients: group I with negative ultrafiltration (UF) (n=14) and group II with positive UF (n=6). In the studied groups peritoneal equilibration test (PET) was done, then the assessment of peritoneal water transport was performed using 125I-HSA as dialysate volume marker, and finally the velocity of peritoneal transport of small molecules expressed by solute mass transport rate (SMTR) coefficient was measured. Patients from both groups belonged to the same category of high-average transporters according to PET criteria. RESULTS: On the base of broaden assessment of peritoneal transport of water and substances it was proved that different, "therapeutic approach" should be applied in studied groups to reach the adequate dialysis. Although in group II the minor modification of continuous ambulatory peritoneal dialysis (CAPD) regimen was desired, the radical change of CAPD schedule or transfer to automated peritoneal dialysis was necessary in cases of patients from group I. CONCLUSIONS: The results of the study indicate that the extended assessment of peritoneal transport kinetics of water and substances increases the capabilities of individualisation of PD program. Therefore, it should be treated as an important element of integrated dialysis care.

Comparison of peritoneal equilibration test with 99mTc-DTPA excretion in the assessment of peritoneal permeability.

Assessment of peritoneal permeability is necessary for successful management of end-stage renal disease (ESRD) patients by continuous ambulatory peritoneal dialysis (CAPD). The objective of this study was to develop an alternative method of assessing the peritoneal permeability and to compare this method with the conventional method, the peritoneal equilibrium test, first described by Twardowski in 1987. Twenty patients undergoing regular CAPD were included in this study. Before starting the peritoneal dialysis, 370 MBq (10 mCi) technetium-99m diethylene triamine penta-acetic acid ((99m)Tc-DTPA) was injected intravenously. A standard dose of the same quantity was kept and used later for calculations. At the end of 4 h, a dialysate fluid sample (1 ml) was collected and the total dialysis effluent fluid volume was measured. Excretion of (99m)Tc-DTPA into the dialysate fluid as a percentage of the injected dose was calculated. Simultaneously, standard peritoneal equilibrium test values were recorded for comparison. Peritoneal excretion of (99m)Tc-DTPA ranged from 8% to 25% of the injected dose, depending on the peritoneal membrane permeability. When the results were compared with the conventional method, a good correlation (r=0.79) was found. This innovative radionuclide technique is a simple and convenient method to assess the peritoneal membrane permeability and can be used as an alternative to the peritoneal equilibrium test, which is very cumbersome and associated with many limitations.

Peritoneal function and assessment of reference values using a 3.86% glucose solution.

BACKGROUND: The most widely used peritoneal function test, the peritoneal equilibration test (PET), is performed with a 2.27% glucose solution. Recently, the International Society for Peritoneal Dialysis committee on ultrafiltration failure (UFF) advised performing the test with 3.86% glucose solution because it is more sensitive for detecting clinically significant UFF. Because no reference values for this test were available, we analyzed the results of standard peritoneal permeability analyses (SPAs) using 3.86% glucose. METHODS: The tests were performed in our center on 154 clinically stable peritoneal dialysis (PD) patients that were free of peritonitis for at least 4 weeks. For the assessment of reference values, we used two approaches. In approach A, patients with UFF, defined as net ultrafiltration (UF) < 400 mL/4 hours, were excluded. In approach B, only patients within their first 2 years of PD treatment were included, regardless of net UF. Means and 95% confidence intervals (95% CI) were calculated for the transport parameters of the PET and SPA. RESULTS: Means of normal distribution with 95% CI in approach A were as follows: for 2.0-L exchanges, mass transfer area coefficient (MTAC) for creatinine 8.8 mL/minute (4.7 - 12.7 mL/min), dialysate/plasma ratio (D/P) creatinine 0.70 (0.52 - 0.88), glucose absorption 58% (44% - 72%), dialysate240/initial dialysate ratio of glucose (Dt/D0) 0.28 (0.18- 0.38), net UF 675 mL (375 - 975 mL), and maximal dip in D/P sodium after correction for diffusion from the circulation 0.110 (0.050 - 0.164); for 1.5-L exchanges, MTAC creatinine 7.4 mL/min (3.8 - 11.0 mL/min), D/P creatinine 0.69 (0.52 - 0.86), glucose absorption 62% (52% - 72%), Dt/D0 glucose 0.25 (0.17- 0.32), net UF 551 mL (430 - 670 mL), and maximal dip D/P sodium 0.120 (0.048 - 0.166). In approach B, most of the transport values were similar; however, values for lymphatic absorption were significantly higher [1.52 mL/min (2-L) and 1.40 mL/min (1.5-L), p < 0.01] and values for the maximum dip in D/P sodium were lower [0.101 (2-L) and 0.112 (1.5-L), p > 0.05]. This was probably the result of including patients with UFF in approach B, since these parameters can be causative factors of UFF. CONCLUSIONS: A peritoneal transport function test using 3.86% glucose provides data on various aspects of transport. This study gives normal reference values that can be used for analysis of causes of UFF.

Assessment of liposome delivery using scintigraphic imaging.

Scintigraphic imaging is a valuable tool for the development of liposome-based therapeutic agents. It provides the ability to non-invasively track and quantitate the distribution of liposomes in the body. Liposomes labeled with technetium-99 m (99mTc) are particularly advantageous for imaging studies because of their favorable physical characteristics. Examples of how scintigraphic imaging studies have contributed to the evaluation and development of a variety of liposome formulations will be presented. These include liposomes for targeting processes with inflammation associated increased vascular permeability such as healing bone fractures and viral infections; liposomes for intraarticular delivery; and liposomes for delivery of agents to lymph nodes located in the extremities, the mediastinum and the peritoneum. Scintigraphic studies of liposome distribution are very informational and often suggest new drug delivery applications for liposomes.