Search PubMed⌕ Search

Biomedical subjects

D G Oreopoulos

Publications and source records attributed to D G Oreopoulos.

At least 19 recordsLinked to original sources
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↗
PubMed1998

Sclerosing peritonitis in continuous ambulatory peritoneal dialysis patients: one center's experience and review of the literature.

Sclerosing peritonitis (SP) is a severe life-threatening condition for patients undergoing continuous ambulatory peritoneal dialysis (CAPD). This report reviews our experience and that reported in the literature concerning the prevalence of SP in CAPD patients, predisposing factors, and in particular, the role of peritonitis, its clinical presentation, diagnosis, treatment, and prevention. A total of 1,288 end-stage renal disease (ESRD) patients entered our peritoneal dialysis (PD) program between September 1977 and September 1997, seven of whom (0.54%) developed SP. The annual incidence of SP was 0.37 per 1,000 patient years, male-to-female ratio was 2.5 (M/F:5/2), mean age was 39+/-16 (median, 37; range, 23 to 61) years, and the median duration on CAPD was 62 (range, 12 to 144) months. Five patients were on CAPD for > or =4 years and two for less than 4 years before they were diagnosed with SP. All SP patients presented with clinical symptoms suggestive of intestinal obstruction, and five patients had decreased solute or fluid removal and had to increase the daily dialysate volume (3/7) or the tonicity of the fluid (4.25%) (3/7) or to combine a regular hemodialysis (HD) session with CAPD (2/7). There was a mean weight loss of 5+/-6 (median, 2; range, 0 to 18) kg. All patients had an episode of peritonitis at a mean time of 2+/-1 (median, 1; range, 1 to 3) months before the diagnosis of SP. The peritonitis was due to Staphylococcus aureus in four and Staphylococcus epidermidis, fungi, and Escherichia coli in one each. The definitive diagnosis of SP was established by laparotomy in four patients or postmortem examination in one patient, while in the remaining two there was no surgical confirmation; however, we believe the diagnosis was extremely likely because of the presence of clinical and radiologic criteria for SP. After the diagnosis of SP, all patients had their catheters removed, CAPD was discontinued permanently, and they were transferred to HD. Although there are isolated case reports of successful outcomes after surgical intervention, especially in patients in whom a peritoneal "cocoon" is related to severe peritonitis, usually the prognosis following surgery is poor. Treatment with immunosuppressive agents has been reported to be beneficial in the treatment of SP, although this has not been confirmed by all investigators. Among our SP patients, five (72%) died of sepsis (3/5) in a mean period of 10+/-5 (median, 9; range, 6 to 17) months after the diagnosis of SP and two are still alive on HD. SP is a rare but serious complication of CAPD. Severe peritonitis, especially in patients on dialysis for more than 4 years, may lead to SP As the prevalence of SP increases in patients on long-term CAPD, early detection is important because of the high morbidity and mortality associated with this condition.

Adult↗
PubMed1998

Peritoneal urea and creatinine clearances in continuous peritoneal dialysis patients with different types of peritoneal solute transport.

We studied whether anuric subjects on continuous ambulatory peritoneal dialysis (CAPD) who achieve the target Kt/V urea of 2.0 weekly will also achieve the target normalized creatinine clearance (NCCr) of 60 liter/1.73 m2 weekly, and the reasons of discrepancy between the two clearances in anuric subjects, by analyzing 476 clearance studies performed in 309 CAPD patients within 12 months of the performance of a peritoneal equilibration test (PET). On the basis of the PET, peritoneal solute transport was classified as low (37 clearance studies), low-average (199 studies), high-average (186 studies) and high (54 studies). We found that weekly values of Kt/V urea in the low transport group (LTG) was 1.74 +/- 0.51, in the low-average transport group (LATG) was 1.66 +/- 0.41, in the high-average transport group (HATG) 1.68 +/- 0.41, and in the high transport group (HTG) 1.73 +/- 0.46 (NS, variance analysis). Weekly values for NCCr, liter/1.73 m2 were: LTG, 37.8 +/- 9.0; LATG, 44.0 +/- 9.2; HATG, 49.2 +/- 10.0; HTG 56.8 +/- 13.3 (P < 0.0001). The ratios of raw (not-normalized) peritoneal creatinine clearance to peritoneal urea clearance were: LTG, 0.65 +/- 0.14; LATG, 0.76 +/- 0.09; HATG, 0.84 +/- 0.09; HTG, 0.91 +/- 0.12 (P < 0.0001). Linear regression with Kt/V urea as x and NCcr as y revealed the following results: LTG, y = 19.486 + 10.500x, r = 0.591 [if x = 2.0, y = 15.004 + confidence interval (95% CI) of y 25.3 to 55.7]; LATG, y = 15.0004 + 17.482x, r = 0.774 (if x = 2.0, y = 50.0, 95% CI of y 38.4 to 61.6); HATG, y = 15.285 + 20.162x, r = 0.829 (if x = 2.0, y = 55.6, 95% CI of y 44.4 to 66.8); HTG, y = 14.945 + 24.134x, r = 0.839 (if x = 2.0, y = 63.2, 95% CI of y 48.4 to 78.1). Peritoneal solute transport type has a major effect on peritoneal creatinine clearance, but an insignificant effect on peritoneal urea clearance. Consequently, the majority of anuric patients who achieve a weekly Kt/V urea of 2.0 will have a weekly NC cr lower than 60 liter/1.73 m2 and will require a Kt/V urea much higher than 2.0 to achieve the target NCcr of 60 liter/1.73 m2 weekly. The current targets of urea and creatinine clearance are not compatible in anuric patients on CAPD.

Adult↗
PubMed1998

Elevation of whole-blood glutathione in peritoneal dialysis patients by L-2-oxothiazolidine-4-carboxylate, a cysteine prodrug (Procysteine).

Glutathione is a major cellular antioxidant that protects protein thiols and inhibits cellular damage due to oxygen free radicals. It has been reported previously that patients undergoing dialysis have low levels of blood glutathione, which may lead to increased susceptibility to oxidant stress. L-2-oxothiazolidine-4-carboxylic acid (OTZ) is a cysteine prodrug that raises cellular glutathione levels by increasing delivery of cysteine, the rate-limiting substrate for glutathione synthesis. This study investigates the effect of OTZ on blood glutathione in a blinded, placebo-controlled study of patients with chronic renal failure treated by peritoneal dialysis. Twenty patients were randomly selected to receive OTZ (0.5 g three times a day orally with meals) or placebo for 14 d. Patients visited the clinic for predose blood collection and safety evaluation at baseline (days 3, 7, and 14 and again at 14 d from the last dose [follow-up]). Glutathione concentrations were determined in whole blood by HPLC. OTZ resulted in a significant rise in whole-blood glutathione at days 7 (594 +/- 129 mumol/L) and 14 (620 +/- 108 mumol/L) compared with baseline (544 +/- 139 mumol/L) (P < 0.01 and P < 0.05, respectively). Glutathione was also significantly increased at days 7 and 14 when normalized by hematocrit (Hct) or hemoglobin to correct for anemic status (e.g., 20.7 +/- 5.7 mumol/L per % Hct [day 7] and 20.9 +/- 4.0 mumol/L per % Hct [day 14] versus 18.0 +/- 4.2 mumol/L per % Hct [baseline]; P < 0.05). Glutathione levels did not change in the placebo group at any patient visit, and levels in the OTZ-treated group returned to baseline at follow-up. There were no serious adverse events attributable to OTZ, and the drug appeared to be well tolerated by patients with renal failure treated by continuous ambulatory peritoneal dialysis. Our results show that OTZ increases blood glutathione levels, which may improve antioxidant status in dialysis patients.

Administration, Oral↗
PubMed1998

Increased peritoneal membrane transport is associated with decreased patient and technique survival for continuous peritoneal dialysis patients. The Canada-USA (CANUSA) Peritoneal Dialysis Study Group.

The objective of this study was to evaluate the association of peritoneal membrane transport with technique and patient survival. In the Canada-USA prospective cohort study of adequacy of continuous ambulatory peritoneal dialysis (CAPD), a peritoneal equilibrium test (PET) was performed approximately 1 mo after initiation of dialysis; patients were defined as high (H), high average (HA), low average (LA), and low (L) transporters. The Cox proportional hazards method evaluated the association of technique and patient survival with independent variables (demographic and clinical variables, nutrition, adequacy, and transport status). Among 606 patients evaluated by PET, there were 41 L, 192 LA, 280 HA, and 93 H. The 2-yr technique survival probabilities were 94, 76, 72, and 68% for L, LA, HA, and H, respectively (P = 0.04). The 2-yr patient survival probabilities were 91, 80, 72, and 71% for L, LA, HA, and H, respectively (P = 0.11). The 2-yr probabilities of both patient and technique survival were 86, 61, 52, and 48% for L, LA, HA, and H, respectively (P = 0.006). The relative risk of either technique failure or death, compared to L, was 2.54 for LA, 3.39 for HA, and 4.00 for H. The mean drain volumes (liters) in the PET were 2.53, 2.45, 2.33, and 2.16 for L, LA, HA, and H, respectively (P < 0.001). After 1 mo CAPD treatment, the mean 24-h drain volumes (liters) were 9.38, 8.93, 8.59, and 8.22 for L, LA, HA, and H, respectively (P < 0.001); the mean 24-h peritoneal albumin losses (g) were 3.1, 3.9, 4.3, and 5.6 for L, LA, HA, and H, respectively (P < 0.001). The mean serum albumin values (g/L) were 37.8, 36.2, 33.8, and 32.8 for L, LA, HA, and H, respectively (P < 0.001). Among CAPD patients, higher peritoneal transport is associated with increased risk of either technique failure or death. The decreased drain volume, increased albumin loss, and decreased serum albumin concentration suggest volume overload and malnutrition as mechanisms. Use of nocturnal cycling peritoneal dialysis should be considered in H and HA transporters.

Adult↗
PubMed1998

Hernia development in CAPD patients and the effect of 2.5 l dialysate volume in selected patients.

The aim of this study was to estimate the prevalence of hernia formation in CAPD patients and to study the effect of increased dialysate volume (2.5 l) in selected population of patients who could tolerate it. We reviewed the charts of 454 individuals treated with CAPD in our center during a five-year period (September 1991-September 1996). Out of 404 patients who used 2.0 l dialysate exchange volume forty-nine (11%) developed hernia (umbilical 53%, inguinal 33%, incisional 14%) after having been on CAPD for an average of 10 +/- 11 months, while only one of the 50 patients who would tolerate 2.5 l developed a hernia (inguinal 2%), after having been on CAPD for 12 months. All hernias were repaired surgically and most of the patients returned to CAPD after temporary intermittent peritoneal dialysis. Age, sex, nutritional status, polycystic kidneys, and diabetes do not seem to be predisposing factors for hernia formation, while previous operation for aortic abdominal aneurysm repair, or low body weight (< 60 kg) were risk factors. The use of increased dialysate volume (2.5 l) in patients who could tolerate it, did not result in a higher frequency of hernia development. Surprisingly, patients with hernias seem to have a higher mortality than those without.

Adult↗
PubMed1997

In vitro simulation of the effect of peritoneal dialysis solution on mesothelial cells.

All previous in vitro biocompatibility tests of peritoneal dialysis fluids have shown that these have inhibitory effects on the function of peritoneal mesothelium. This report presents results from in vitro experiments performed to study the effect of dialysis fluids (Dianeal 1.36 and Dianeal 3.86; Baxter, Round Lake, IL) on the function of mesothelial cells under conditions that simulate the in vivo state of these solutions in the peritoneal cavity. Thus, cells were initially exposed only to the unused fluids that were thereafter gradually diluted (over 4 hours) with pooled effluent dialysate from continuous ambulatory peritoneal dialysis patients. During the following 20 hours, cells were incubated in a mixture of unused fluid (10% vol/vol) and dialysate effluent (90% vol/vol). The mesothelial cells exposed to dialysis fluids under such conditions became activated cells compared with exposed to dialysate effluent (control) alone. Thus, synthesis by mesothelial cells of all tested substances was enhanced during exposure of the mesothelium to the dialysis fluids: interleukin-6: Dianeal 1.36, +257%; Dianeal 3.86, +181% (both P < 0.05); hyaluronic acid: Dianeal 1.36, +72%; Dianeal 3.86, +63% (both P < 0.05); tissue plasminogen activator: Dianeal 3.86, +33% (P < 0.05); and plasminogen activator/inhibitor-1: Dianeal 1.36, +28%; Dianeal 3.86, +38% (both P < 0.05). Our results show that the peritoneal mesothelium becomes activated when it is exposed to acidic, hyperosmotic dialysis fluids diluted with the dialysate effluent, in a manner that imitates the in vivo changes in these solutions during their intraperitoneal dwell.

Cells, Cultured↗