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Biomedical subjects

D G Oreopoulos

Publications and source records attributed to D G Oreopoulos.

At least 37 records · Page 2Linked to original sources
PubMed2001

Excessive weight gain during peritoneal dialysis.

The authors carried out a retrospective chart review in 114 patients treated for at least two years at the Toronto Western Hospital Peritoneal Dialysis Unit and identified eight, who gained an "excessive" amount of weight equal to or greater than 10 kg of their initial weight. These patients had gained an average of 13.1 kg over the preceding two years. They are mostly males and their average age is 51 years. They are well-nourished normotenseive nondiabetics with mostly normal cardiac function. They are adequately dialyzed (per KT/V urea), have little residual renal function and typically have peritoneal membranes characterized by high average transport. According to BIA analysis, this weight gain was likely due to an increase in fat mass accompanied by a trend toward decreasing body-cell mass. This weight gain may be due to increased caloric intake secondary to dialysate glucose absorption in the setting of high average (peritoneal membrane) transport. Such excessive weight gain also may occur if these patients have polymorphism of the UCP-2 gene, which can alter metabolic rate.

Adult↗
PubMed2001

A comparison of the biocompatibility of phosphate-buffered saline and dianeal 3.86% in the rat model of peritoneal dialysis.

Phosphate-buffered saline (PBS), an isotonic solution with a physiologic pH can be considered an example of a biocompatible dialysis fluid. This study compared the biocompatibility of PBS with that of Dianeal 3.86% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.), using a model of peritoneal dialysis in the rat. In an acute experiment, after catheter implantation, rats were infused on day 1 with PBS, on day 5 with standard dialysis solution (Dianeal 3.86%), and on day 7 again with PBS. When rats were injected with Dianeal 3.86%, the inflammatory reaction was suppressed as compared with PBS. The cell count was lower with Dianeal (-85%, p < 0.001), the neutrophil:macrophage ratio in dialysate was 80% lower (p < 0.01), total protein concentration in the Dianeal dialysate was 73% lower (p < 0.01), and the dialysate nitrite level was 45% lower (p < 0.01). In a chronic experiment, after catheter implantation, rats were dialyzed for four weeks with PBS or with Dianeal 3.86%. At the end of the study, a 1-hour peritoneal equilibration test (PET) was performed. As evaluated on a semiquantitative scale, macroscopic changes in the peritoneum were more severe in rats exposed to PBS than in those exposed to Dianeal 3.86% (8.6 +/- 3.2 vs 5.2 +/- 2.6, p < 0.05). The thickness of the visceral peritoneum was comparable in both groups; but, in PBS-treated rats, the peritoneal interstitium contained more inflammatory cells and more new vessels. During the 1-hour PET, peritoneal permeability to water and solutes was comparable in the two groups. Despite a more physiologic composition, PBS is a less biocompatible peritoneal dialysis solutions than is standard, acidic, hypertonic dialysis solution.

Animals↗
PubMed2001

Prevention of catheter related infections in patients on CAPD.

Catheter-related infections remain a serious problem for patients on peritoneal dialysis. Such infections can be reduced by careful patient selection and training, by the use of the best connection technology and screening and treating nasal carriage. To date, treatment is less than optimal and therefore, the primary goal should be prevention of catheter-related infections. Prevention is based on improving catheter design and implantation technique, while providing careful exit-site care. Regardless of how it is implemented, we must aggressively pursue the prevention of catheter-related infections by eradicating S. aureus exit-site carriage in PD patients. Based on its effectiveness in adult PD patients, its low rate of adverse effects, and its reasonable cost-effectiveness, application of mupirocin ointment at the exit-site is the current method of choice for preventing PD catheter infections caused by S. aureus. In addition to reducing S. aureus exit-site infections, mupirocin seems to reduce the rates of staphylococcal peritonitis and PD catheter loss. Whether the ointment should be applied in the nares, to the exit-site or both, and whether it should be used only in staphylococcal nasal carriers or all PD patients requires further study.

Anti-Bacterial Agents↗
PubMed2001

Morphologic aspects of chronic peritoneal dialysis in a rat model.

OBJECTIVE: We previously put forward an experimental model for evaluating peritoneal function in chronically dialyzed rats. In the present paper, we show the morphologic alterations detected by electron microscopy in the peritonea of chronically dialyzed rats. MATERIALS AND METHODS: The study was done in male Wistar rats. Animals were divided into two groups: control (non dialyzed) rats and dialyzed rats [intraperitoneally exposed to Dianeal 3.86% (Baxter Healthcare Corporation, Deerfield, IL, U.S.A.) for 1 month]. At the end of the study, the rats were humanely killed by bleeding, and samples of the visceral peritoneum covering the liver were taken from 3 rats in each group. The samples were examined by transmission electron microscopy (TEM). RESULTS: In control rats, the peritoneum was composed of flattened mesothelial cells covering the thin layer of the submesothelial connective tissue (ST), containing few fibroblasts. In dialyzed animals, a dramatic expansion of the ST was found. We saw compartmentalization of the ST, with changed morphology of the fibroblasts, altered organization of collagen fibers, and changes in the cells infiltrating the ST. Apart from the fibroblasts, mast cells were relatively numerous. CONCLUSIONS: Our work underlines the capabilities of morphology studies in an animal model for assessing peritoneal dialysis fluid biocompatibility.

Animals↗
PubMed2001

Comparison of the biocompatibility of phosphate-buffered saline alone, phosphate-buffered saline supplemented with glucose, and dianeal 3.86%.

OBJECTIVE: We compared the effects of intraperitoneal infusion of phosphate-buffered saline (PBS, pH 7.4), of PBS supplemented with 3.86% glucose (G), and of standard dialysis solution [Dianeal 3.86%: Baxter Healthcare Corporation, Deerfield, IL, U.S.A. (D)] on intraperitoneal inflammation in dialyzed rats. METHODS: After catheter implantation, rats were infused on day 1 with PBS, on day 3 with PBS+G, on day 5 with D, and on day 7 again with PBS (PBS-2). After a 4-hour dwell, dialysate samples were collected and analyzed. RESULTS: All dialysate parameters studied [dialysate cell count, neutrophil:macrophage ratio (Ne:Ma), and total protein], except tumor necrosis factor alpha (TNFalpha), were comparable during both PBS infusions. During dialysis with PBS+G, the inflammatory response was suppressed as compared with the first dialysis with PBS (cell count, p < 0.001; Ne:Ma, p < 0.05; TNFalpha, p < 0.001; total protein, p < 0.001). During dialysis with D, peritoneal inflammatory parameters were further suppressed (cell count, p < 0.001 vs PBS and p < 0.01 vs PBS+G; Ne:Ma, p < 0.001 vs PBS and p < 0.05 vs PBS+G; TNFalpha, p < 0.001 vs PBS and p < 0.001 vs PBS+G; total protein, p < 0.001 vs PBS and p < 0.01 vs PBS+G). CONCLUSIONS: Hypertonicity of the dialysis fluid suppresses intraperitoneal inflammatory parameters in rats. The suppression was even more severe when Dianeal 3.86% was used. That finding could be due to the low pH and presence of GDPs in the fluid.

Animals↗
PubMed2000

Dialysis solution containing hyaluronan: effect on peritoneal permeability and inflammation in rats.

BACKGROUND: Hyaluronan (HA), a high molecular weight mucopolysaccharide found in interstitial tissues and fluid, is lost from the peritoneal cavity during peritoneal dialysis. In order to determine the role of HA in peritoneal function, we investigated the effects of exogenous HA on peritoneal permeability, markers of intraperitoneal inflammation, and peritoneal morphology in rats exposed to peritoneal dialysis solution for four weeks. METHODS: Wistar rats were infused intraperitoneally, twice daily, with conventional, hypertonic dialysis solution (Dianeal 3.86%; control) or Dianeal solution containing 10 mg/dL of high molecular weight HA. Peritoneal permeabilities and clearances of solutes and protein were determined using a modified peritoneal permeability test (peritoneal equilibration test) at the beginning and the end of the treatment. Peritoneal volume and ultrafiltration were determined using a macromolecular marker and by gravimetric methods. Peritoneal inflammation was determined by cell counts and differential and by the measurement of cytokine concentrations in the dialysate effluent. Peritoneal thickness and HA content were determined in liver and mesentery biopsies taken at the end of the experiment. RESULTS: After four weeks of exposure to the dialysis solution, transperitoneal protein equilibration was significantly lower in HA-treated rats compared with rats treated with Dianeal alone (46% lower for albumin, P < 0.003; 33% lower for total protein, P < 0.001). The total drained volume after a four hour dwell was 29% higher in the HA group compared with the control (P < 0.001), yielding a positive net ultrafiltration in the HA group versus a negative net ultrafiltration in controls. Peritoneal clearances of urea and creatinine tended to be elevated in HA-treated rats, while clearances of total protein and albumin tended to be lower. Dialysate effluent from rats exposed to HA contained a lower percentage of neutrophils (8.8 +/- 22.8 +/- 9.5%, P < 0.01) and lower levels of the cytokines, tumor necrosis factor-alpha (11.2 +/- 14.7 vs. 42.3 +/- 35.3 pg/mL, P < 0.05) and monocyte chemoattractant protein-1 MCP-1 (72.0 +/- 86.5 vs. 402.4 +/- 258.3 pg/mL, P < 0.02), compared with rats treated with Dianeal alone. The thickness of the peritoneal interstitium showed a similar increase in both groups, but mesenteric tissue from the HA group contained more HA (48%, P < 0.01) than tissue from control animals. CONCLUSIONS: The addition of HA to peritoneal dialysis solution decreases protein permeability, increases ultrafiltration, and decreases cytokine levels and the proportion of peritoneal neutrophils in dialysate from rats exposed to hypertonic dialysis solution. These results suggest that exogenous HA may help to protect the peritoneal membrane during exposure to dialysis solutions. These benefits, if sustained in the clinical setting, could lead to improvements in the therapy of peritoneal dialysis.

Animals↗
PubMed2000

Peritoneal dialysis in the next millennium.

The main thrust of research will be the prevention of renal disease and its progression to the end-stage state (ESRD); such efforts will reduce or even reverse the present epidemic of ESRD by the middle of the 21(st) Century. In the meantime, the number of ESRD patients will continue to increase and, unless xenotransplantation and cloning of one's own kidneys using stem cells will provide an alternative, the various modes of dialysis will continue to be the principle treatment for an increasing numbers of ESRD patients. Peritoneal dialysis (PD) has achieved success at certain salient points and, to advance further, the next generation of nephrologists will have to build on these. They include the following: PD is the treatment of choice for children; it has low rates of peritonitis; it has similar (or in some countries, better) survival rates than hemodialysis; it has lower costs; it has adequate clearances through the introduction of automated PD; and it is an effective treatment for those awaiting a kidney transplant. This report presents the authors' views concerning the areas in which PD will improve in the future. These include (1) a reduction in technique failure rates that will allow us to maintain a larger number of patients on PD for 10 years or more; (2) prevention of long-term changes of the peritoneal membrane through the use of more "friendly" solutions; (3) prevention of malnutrition; (4) the development of better peritoneal access devices; and (5) the increased use of PD as the treatment of first choice for most ESRD patients.

Humans↗
PubMed2000

Patients on chronic peritoneal dialysis for ten years or more in North America.

Thirty-six patients on peritoneal dialysis (PD) for more than ten years in six North American centers were analyzed retrospectively. In the six centers, the percentage of patients surviving for more than ten years varied between 0.8% and 7.3%. The study group included 27 females and 9 males aged 38.6 +/- 14.2 years [mean +/- standard deviation (SD)] at the start of treatment. Of the 36 patients, 28 were Caucasian. The most common cause of end-stage renal disease (ESRD), present in 12 patients, was chronic glomerulonephritis. Only 4 patients had diabetes. At the beginning of the study, 19 patients had hypertension (the most common comorbid condition); 11 had no comorbid conditions at the start. Creatinine clearance at the start was 4.12 +/- 3.5 mL per minute, and the mean duration to anuria was 51 +/- 25 months. Mean initial body weight was 55 +/- 9 kg, and mean body surface area was 1.5 +/- 0.2 m2. Serum albumin levels showed an increase from 33.8 +/- 3.6 g/L at the start of the study to 38.2 +/- 3.9 g/L at the end. Hospitalization rate was low at 0.5 +/- 0.3 admissions per patient-year, and duration of hospitalization was 4.8 +/- 3.7 days per patient-year. Peritonitis was the most common cause of hospitalization. The mean peritonitis rate was 1 episode every 52 +/- 48 patient-months. There were 36 catheter changes in 18 patients; 16 patients had a single PD catheter throughout the period of study. Autonomous hyperparathyroidism was the most common long-term complication. At the end of the study period, 11 patients were still on PD, 9 had died, 5 had been transferred to hemodialysis (HD), 1 was alive with a functioning allograft, and 1 was lost to follow-up. We conclude that patients who survive longer than ten years on PD are most likely to be young Caucasian females, small in body size, who are non diabetic, with few comorbid conditions. These long-term survivors have few hospitalizations, and their peritonitis rate is low. In this group of patients, severe autonomous hyperparathyroidism is the most common long-term complication.

Adolescent↗
PubMed2000

Hypertonicity of dialysis fluid suppresses intraperitoneal inflammation.

We studied acute and chronic intraperitoneal inflammation during dialysis performed in rats injected with phosphate-buffered saline alone (PBS) or PBS supplemented with glucose (Glu) or with mannitol (Man). In acute experiments, the result of a first dialysis with PBS in every rat (dialysis I) was compared with a second dialysis performed 24 hours later (dialysis II) using a different dialysis fluid: either PBS with 3.86 g/dL Man or PBS with 3.86 g/dL Glu. In rats exposed to hypertonic dialysis solutions (both Glu and Man), inflammatory reaction was decreased (cell count: p < 0.05; nitric oxide secretion: p < 0.05; protein in dialysate: p < 0.05). In control animals treated only with PBS (dialysis I and dialysis II), the inflammatory reactions during dialysis I and dialysis II were comparable. In chronic experiments, rats were dialyzed with the tested fluids for four weeks. Weekly, dialysate samples were taken and analyzed. At the end of the study, cell counts and protein losses were higher in the PBS-treated rats than in the other groups (cell count: p < 0.05, Glu vs PBS, and p < 0.05, Man vs PBS; protein in dialysate: p < 0.001, Glu vs PBS, and p < 0.01, Man vs PBS). We conclude that hypertonicity of the dialysis fluid inhibits the inflammatory reaction in the peritoneal cavity during peritoneal dialysis.

Acute Disease↗
PubMed2000

Encapsulating peritoneal sclerosis: definition, etiology, diagnosis, and treatment. International Society for Peritoneal Dialysis Ad Hoc Committee on Ultrafiltration Management in Peritoneal Dialysis.

Current definitions of encapsulating peritoneal sclerosis are practical and clinically relevant. It is important to adhere to a more uniform use of the proper terminology, and it is the recommendation of the authors that EPS be adopted as the more appropriate term. The best literal definition of EPS is based on clinical-pathologic criteria. Differentiation of EPS from the general category of ultrafiltration failure is required. Further, better appreciation of the diverse pathways that can lead to the same final common clinical-pathologic picture should not be overshadowed by the requirement of uniform terminology. Incidence and prevalence of the syndrome have been defined in some large populations and a few single-center experiences. The former show an incidence of less than 1%, while higher percentages are reported in the latter. The reported increased incidence with duration on therapy requires validation. The epidemiology of the syndrome offers limited insight into its pathogenesis. A list of factors, both dialysis-related and non dialysis-related. has been accumulated. Except in a few categories where agents are clearly related to the development of EPS, the majority of the listed factors for dialysis-related BPS remain, at best, associations and at worst, simple conjecture. The same limitations that plague the issue of etiology apply in the area of pathogenesis. More basic, focused work is required. The diagnosis of EPS remains based on clinical suspicion confirmed with, primarily, radiologic findings. Pathologic confirmation is obtained in cases that come to surgery for management or for catheter removal. Radiologic studies are precise enough for confirmation, but none have been evaluated for early diagnosis for possible early intervention or prevention. Studies based on transport characteristics or effluent dialysate constituents are not useful for EPS. At present, there are no reliable predictive tests for BPS that can be used in individual patients. Therapy of BPS is based on anecdotal evidence. The possible variable etiologies and probable distinct pathways leading to the syndrome may make a uniform therapeutic approach unlikely. Further, the limited number of cases and the sporadic pattern of occurrences make therapeutic trials not readily feasible. This is distinct from the case of ultrafiltration failure, where significant advances in mechanism elucidation and rationale-based interventions have been made.

Humans↗
PubMed1999

l-2-oxothiazolidine-4-carboxylic acid modulates function of peritoneal mesothelial cells in vitro.

The influence of the glutathione precursor, l-2-oxothiazolidine-4-carboxylic acid (OTZ), on the function of human peritoneal mesothelial cells in vitro, in conditions that mimic the in vivo effect of peritoneal dialysis solutions on mesothelium, was studied. Mesothelial monolayers were exposed to dialysis fluids (Dianeal 1.36 or Dianeal 3.86; Baxter Healthcare Corp, Round Lake, IL) that were diluted gradually with pooled-effluent dialysate obtained from patients undergoing continuous ambulatory peritoneal dialysis. In vitro exposure of mesothelium to standard dialysis fluid enhances their susceptibility to injury by hydrogen peroxide. OTZ added to dialysis solution in concentrations of 1 mmol/L prevented the toxic effect of hydrogen peroxide, probably by increasing intracellular glutathione. Mesothelial cells exposed to dialysis fluid become activated, evidenced by increased release of interleukin-6 and hyaluronan. OTZ used in concentrations of 1 mmol/L reduced that effect. Furthermore, the addition of glucose to the culture medium in a concentration of 45 mmol/L inhibits the proliferation of mesothelial cells; the presence of OTZ, 1 mmol/L, partially prevents the inhibitory effect of glucose. The results presented in this report show that by augmenting the intracellular concentration of glutathione in mesothelial cells by the addition of OTZ to the dialysis fluid, we can increase their resistance to the acute toxicity of free radicals and long-term toxicity of glucose. In addition, mesothelial cells with an increased glutathione level are less activated after their exposure to dialysis fluid.

Cell Division↗
PubMed1999

The relation between body size and normalized small solute clearances in continuous ambulatory peritoneal dialysis.

The normalized peritoneal clearances of small solutes depend on the ratio of their concentration in dialysate and plasma (D/P) and the drain volume (Dv) corrected for some measure of body size such as body water (V) or body surface area (BSA). The clearance formulas (D/P) x (Dv/V) and (D/ P) x (Dv/BSA) can be used to examine why large individuals tend to be underdialyzed. Large people have low normalized drain volumes (Dv/V, Dv/BSA). It is not known whether size affects the D/P ratios. The purpose of this study was to examine the relationship between normalized peritoneal clearances (Kt/Vurea, CCr per 1.73 m2 BSA) and four size indicators (weight, height, V, BSA) in 301 patients on continuous ambulatory peritoneal dialysis (four daily exchanges with 2-L exchange volume) who underwent 613 clearance studies. Highly significant (P < 0.001) nonlinear relationships were found between Kt/Vurea and weight (r2 = 0.371), height (r2 = 0.289), BSA (r2 = 0.436), and V (r2 = 0.527); and between CCr and weight (r2 = 0.178), height (r2 = 0.115), BSA (r2 = 0.199), and V (r2 = 0.151). There were also significant negative correlations between the normalized drain volumes (Dv/V and Dv/BSA) and all four indicators of body size. Raw (not normalized) peritoneal clearances and drain volumes correlated positively with size. However, D/P(urea) or D/P(creatinine) did not vary with any size indicator except for a weak association between D/P(creatinine) and V (r = 0.089, P = 0.028). This association was not confirmed when V was used to stratify subjects into quartiles, and group differences for D/P(creatinine were tested by one-way ANOVA. This study shows that the exclusive cause of the low normalized peritoneal clearances in large subjects on continuous ambulatory peritoneal dialysis is a low normalized drain volume. No evidence was found to indicate that body size influences the D/P ratio of small solutes. The portion of the variance in normalized clearance explained by size varies by size indicator and solute (urea versus creatinine).

Adult↗