PubMed Health⌕ Search

Biomedical subjects

D G Oreopoulos

Publications and source records attributed to D G Oreopoulos.

At least 127 records · Page 7Linked to original sources

In vitro study of the mechanism of potassium transport into human mesothelial cells. I: Effect of hyperosmolality.

OBJECTIVE: To study the mechanism(s) of potassium transport into human mesothelial cells (HMC) exposed to osmotic solutes. DESIGN: Using potassium analog 86Rb, we evaluated its intracellular transport through three pathways: 1. blocked by ouabain; 2. blocked by furosemide but not by ouabain; 3. blocked by neither furosemide nor ouabain. Experiments were performed in a normotonic medium (control) or in a medium supplemented with osmotic solutes (glucose, glycerol, mannitol). Both the acute and chronic effects of osmotic solutes on potassium transport were studied. RESULTS: The acute exposure of mesothelial cells to osmotic solutes modifies the intracellular transport of potassium through all studied channels, and the effect is specific for every solute. In mesothelial cells exposed over 7 days to glucose (90 mM), the intracellular transport via ouabain- and furosemide-blocked channels is decreased, whereas it is increased through the third pathway. Total intracellular accumulation of 86Rb (potassium) ions in mesothelial cells cultured in a medium supplemented with various concentrations of glucose is decreased, and this effect is proportional to the concentration of glucose in the medium. CONCLUSIONS: The intracellular transport of potassium in mesothelial cells is regulated through at least three independent mechanisms. Acute or chronic exposure of mesothelial cells to a hypertonic medium affects the intracellular accumulation of potassium, and this effect is specific for the various osmotic solutes.

Biological Transport↗

Destructive spondyloarthropathy in a patient on continuous ambulatory peritoneal dialysis for 13 years.

Since 1984 there have been reports of a destructive spondyloarthropathy occurring in patients on long-term hemodialysis. The primary abnormality appears to be an accumulation of beta 2-microglobulin, which is not adequately removed by dialysis, and forms amyloid deposits in articular and periarticular tissues. We report a case of this disease in a patient treated only by peritoneal dialysis. While this form of treatment may delay the development of arthropathy, as compared to hemodialysis, it does not prevent it. An increasing incidence of this disorder may be expected, since increasing numbers of patients have been on long-term peritoneal dialysis.

Aged↗

Effects of intraperitoneal infusion of dextrose and amino acids on the appetite of rabbits.

We studied the effect of intraperitoneal infusion of various volumes and concentrations of dextrose (D) and amino acid (AA) solutions, in a variety of peritoneal dialysis schedules on food intake and biochemical profile in normal and uremic rabbits. Following omentectomy, a peritoneal catheter was implanted. Animals had free access to food, and consumption was measured daily by weight of the remaining food in the cage. We studied the effect of volume (30-50-100 mL/kg), dextrose concentration (0.5-1.5-2.5-4.25-6.6 g/dL) and AA (Travasol based) (2% in Dianeal or glucose-free solution). Dialysis schedules included once/day, twice/day, or four-daily exchanges similar to CAPD. The durations of the exchanges were 4-6 weeks and in certain groups, amino acid exchanges for a week alternated with dextrose exchanges. Our results indicate the following: omentectomy and catheter implantation significantly decrease food intake. There is a significant decrease in food intake after initiation of dialysis that returns to baseline after 2-4 weeks while dialysis continues. Higher volumes (100 mL/kg) decrease food intake significantly, especially with hypertonic solution of either D or AA. There was no difference in food intake between D and AA infusion in any amount of infused volumes. Amino acids do not seem to have a suppressing effect on appetite. However, large volumes and hypertonicity reduce food intake.

Amino Acids↗

An animal model for the study of amino acid metabolism in uremia and during peritoneal dialysis.

We tried to determine the suitability of the rabbit as an animal model to study amino acid (AA) metabolism in continuous ambulatory peritoneal dialysis. We also measured the effect of intraperitoneal (ip) infusion of AA on blood AA changes and food consumption. Plasma AA levels were measured in 10 normal rabbits after an overnight fasting and 30, 60, and 120 minutes after a meal. Following these baseline observations, rabbits were randomly divided into two groups. One group of five rabbits was made uremic after surgical partial nephrectomy, whereas the remaining (controls) underwent sham operations. Two weeks after the induction of uremia we measured the effect of chronic renal failure on fasting and postprandial (30, 60, 120 minutes) plasma AA levels. Upon the completion of the second experiment (4 weeks after the induction of uremia) we studied the effect of an ip AA on plasma AA profile 1, 2, 4, and 6 hours after the infusion in both uremic and control rabbits. We also measured the food intake in all experiments. The results of our experiments showed the following: 1. plasma AA in the rabbits decreased after induction of chronic renal failure and increased after food ingestion and ip infusion of AA solution; 2. neither induction of uremia nor ip AA infusion have an effect on food consumption; 3. the majority of the alterations in plasma AA levels we observed in the uremic rabbits were similar to those observed in humans, indicating that the rabbit may be a suitable model for the study of AA metabolism in chronic renal failure and during peritoneal dialysis.

Amino Acids↗

Pruritus in continuous ambulatory peritoneal dialysis and hemodialysis patients.

To study the prevalence and pathogenesis of uremic pruritus, CAPD and HD patients were asked to complete a questionnaire. The replies were quantitated based on numerical scales, and the results were compared with various hematological and biochemical parameters, underlying disease, and duration of dialysis. There were 113 CAPD patients (63 males and 50 females), mean age 60 (range 20-84) years, average time on CAPD 20 (range 1-163) months and 76 HD patients (44 males and 32 females) mean age 57 (range 23-81) years, mean time on HD 44 (range 2-242) months. Replies to questions were evaluated and graded by the same investigator who did not know the patients. Pruritus was present in 70 (62%) CAPD patients (64% in females and 60% in males p = NS) and in 41 (54%) HD patients (69% in females and 43% in males, p = 0.025). Before starting dialysis pruritus was present in 30% CAPD patients and 28% HD patients. Pruritus was graded as mild, moderate and severe; the distribution was 58.6%, 34.3%, and 7.1% (CAPD) and 43.9%, 41.5%, and 14.6% (HD), respectively. Dry skin was reported by 73% CAPD patients and 72% HD patients. This xeroderma was correlated with the severity of pruritus and was also present in 65% CAPD and 48.5% HD patients without pruritus. Patients with pruritus were older than those without pruritus both for CAPD (63 vs 54 years, p = 0.004) and HD (61 vs 51 years, p = 0.003). A significant correlation was observed only between pruritus score and age for CAPD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of erythropoietin treatment on nutritional status of continuous ambulatory peritoneal dialysis patients.

Seventeen patients--10 females, 7 males--mean age 52 years (range: 21-77 years), on CAPD for an average of 35 months (range 10-160 months) were studied. Mean initial dose of EPO was 114 +/- 45 U/kg/week subcutaneously (range: 59-209). The dose was adjusted to achieve and maintain a target Hb of 100 g/L and Hct 30%. Fifteen of the patients (88.2%) achieved this target within 6 months [baseline to month 6 changes: Hb 72 +/- 10 g/L to 107 +/- 12 g/L (p = 0.0001); Hct 22 +/- 3% to 33 +/- 4% (p = 0.0001)]. Serum total protein also increased significantly over the time of EPO use (p = 0.0133); changes from baseline were significant by the fourth month [68 +/- 9 g/L to 72 +/- 9 g/L (p = 0.0115)]. Serum albumin also increased significantly over time (p = 0.0157). The change from the baseline result (37 +/- 4 g/L) was statistically significant by month 2 (p = 0.0060) and was maintained over the following 4 months [month 6 result: 40 +/- 3 g/L (p = 0.0180)]. The increase was greater for 8 patients with initial serum albumin < 35 g/L (mean change 5.75 g/L) than for the 9 subjects with levels > 35 g/L (mean change 0.11 g/L). In a comparison group of 17 patients (matched for age, sex, duration of CAPD, underlying disease and antihypertensive treatment), who did not receive EPO treatment, albumin and protein did not appear to increase over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of erythropoietin on blood pressure in continuous ambulatory peritoneal dialysis patients.

To assess the effect of erythropoietin (EPO) treatment on blood pressure in continuous ambulatory peritoneal dialysis (CAPD) patients, we analyzed in a retrospective study the results of 6 months of EPO treatment in 17 CAPD patients. There were 10 females and 7 males, mean age 52 years, mean duration on CAPD 35 months. They received subcutaneously a mean initial EPO dose of 114 +/- 45 U/kg/week (range 59-209). This dose was adjusted throughout 6 months to achieve and maintain a target Hb of 100 g/L (Hct 30%). Seven of the patients were hypertensive before starting EPO treatment. Fifteen patients (88.2%) achieved the target hemoglobin. For all subjects (n = 17) there was a significant increase in lying mean blood pressure (MBP) from 93.8 +/- 10.0 to 105.2 +/- 14.4 mmHg (p = 0.0024). Four patients required an increase in their antihypertensive medication, and 4 were not treated before we started antihypertensive treatment (Group I). This group represents 46% (8/17) of the patients. There was no change in the antihypertensive medication status of the remaining 9 patients (Group II). The baseline lying MBP was not significantly different for the two groups (98.8 +/- 9.8 mmHg vs 96.1 +/- 7.2 mmHg). The mean weekly dose of EPO during the first 3 months was higher in Group I (126 vs 100 U/kg) and conversely was lower during the last 3 months (mean dose 108 vs 117 U/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Peritoneal catheters and exit-site practices: toward optimum peritoneal access.

The peritoneal catheter is the CAPD patient's lifeline. Advances in catheter knowledge have made it possible to access the peritoneal cavity safely and maintain access over an extended period of time. Infection at the exit site remains a major problem, a solution for which is being extensively researched. The successful outcome of a catheter in an individual depends on meticulous care and adherence to sound principles of catheter insertion and management. The guidelines provided in this publication represent the consensus based on the extensive experience of several major centers worldwide.

Catheters, Indwelling↗

Long-term continuous ambulatory peritoneal dialysis.

Of 174 patients who entered our CAPD program, 58 received transplants, 7 were transferred to another center, one recovered satisfactory kidney function, 22 were transferred to hemodialysis, 24 to IPD, 52 died and 10 remained on CAPD for at least seven years, when this study was completed. These 10 patients (8 women and 2 men) who are described here in detail had a median age of 46 (range of 24 to 63) years at entry. Their primary renal disease was glomerulonephritis (6), polycystic kidney disease (2), nephrosclerosis (1) and Alport's disease (1). They spent 91 to 134 (average 113) months on CAPD. They had a significant (p = 0.025) increase in body weight from 54.5 +/- 2.8 kg to 59.6 +/- 3.0 kg during the first 3 years, and a decrease in ultrafiltration capacity; BUN and serum creatinine remained relatively stable. Mean total protein and serum albumin remained unchanged at 65 and 35 g/l respectively, throughout the study. There were no significant changes in the hemoglobin and lipid values. Renal osteodystrophy progressed slowly. Peritonitis rate in this group was one episode every 18.9 patient months. These 10 patients had a total of 25 catheters implanted during the study period. The average hospitalization rate was 8.76 days per patient year, 5.34 of which were for peritonitis. Of these 10 patients, one was transferred to hemodialysis, 5 died (4 of or during peritonitis, one of myocardial infarction) and 4 remained on CAPD. Our experience with these 10 patients indicates that CAPD can be carried out over long periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Weight↗

Toxicity of osmotic solutes on human mesothelial cells in vitro.

We evaluated the effect of the various osmotic solutes on the growth rate of human mesothelial cells (HMC) in an in vitro culture. Glucose inhibited proliferation of HMC in a dose dependent way. At high glucose concentrations (60 mM, 90 mM) the effect was instant but at lower concentration (30 mM) decrease in the mesothelial cell proliferation was significant only after five days of incubation. Reversibility of the glucose effect was inversely proportional to exposure time to this solute. Mannitol and glycerol studied in similar concentrations as glucose decreased proliferation of the mesothelial cells less than glucose, whereas amino acid glycine had a similar effect to glucose. However, all osmotic solutes caused similar injury to mesothelial cells membrane as measured by release of LDH. These results suggest that the toxic effect of the osmotic solutes on proliferation of the mesothelial cells depends not only on the hyperosmolality but also on some metabolic effect(s). In an in vitro culture, HMC may provide a suitable model for the study of the toxic effect of dialysis fluid on peritoneal mesothelium.

Cell Division↗

Recent developments in peritoneal dialysis.

Significant developments over the past 10 years have established continuous ambulatory peritoneal dialysis as a successful kidney-replacement treatment. Peritonitis rates have fallen, and investigators are attempting to establish objective criteria for adequacy of dialysis. Malnutrition is a serious concern, but short-term experience with intraperitoneal amino acids promises success in the management of this complication. A significant improvement in the well-being of patients with end-stage renal disease was produced by recombinant human erythropoietin, and use of recombinant human growth hormone promises catch-up growth for children receiving long-term peritoneal dialysis treatment. As increasing numbers of patients are maintained on continuous ambulatory peritoneal dialysis over longer periods, we will begin to encounter beta 2-microglobulin-related amyloidosis possibly at the same rate in these patients as in those receiving long-term hemodialysis treatment.

Humans↗

Chondroitin sulphate and peritoneal permeability.

We studied the effect of chronic intraperitoneal (ip) infusion of saline supplemented with the glycosaminoglycan-chondroitin sulphate 0.1% on the permeability and peroxidation of the peritoneal membrane in rats and compared this with the effect of saline infusion alone. Animals treated with chondroitin sulphate had a higher net ultrafiltration (uf), a slower glucose absorption from the dialysate and less trans-peritoneal loss of proteins. Chronic ip infusion of chondroitin sulphate reduced peroxidation of the peritoneum. These observations suggest that chondroitin may effect the peritoneal interstitium-an important barrier of fluid and solutes transport.

Animals↗

CAPD in end stage patients with renal disease due to diabetes mellitus--an update.

Large numbers of diabetics with renal failure have been treated by continuous ambulatory peritoneal dialysis (CAPD). Overall 1-year patient survival varies from 51% to 87%. Mortality is due to cardiovascular disease in more than 50% of the cases. Young diabetics with good blood pressure control and without cardiac disease have a chance at long survival on CAPD. In comparison to hemodialysis, CAPD yields better patient survival for young diabetics and worse for old diabetics, worse technique survival, probably greater overall morbidity, and similar rates of progression of retinopathy, neuropathy and peripheral vascular disease. Adequacy of peritoneal clearance and peritoneal ultrafiltration characteristics are similar between diabetics and non-diabetics on CAPD. CAPD is associated with better preservation of renal function than hemodialysis in diabetics. The rates of CAPD peritonitis do not differ substantially between diabetics and non-diabetics. However, diabetes appears to be associated with higher incidence of tunnel infection. Hyperlipidemia is generally less severe in diabetics than non-diabetics on CAPD, but malnutrition is more frequent in diabetics. CAPD has many attractive features and several drawbacks for the management of diabetics with end stage renal failure (ESRF). Its ultimate success will depend on the outcome of efforts to improve cardiovascular mortality, malnutrition, hyperlipidemia and catheter-related infections.

Adolescent↗

Urea kinetics has limited relevance in assessing adequacy of dialysis in CAPD.

The application of urea kinetics to CAPD is controversial. Additional data is presented from our recent study on this topic. Different methods of calculating KT/V and normalized protein catabolic rate (PCRN) are compared and KT/V is shown to be on average 6.5% higher when V is calculated by Watson's formulae instead of by body weight alone. This discrepancy increases with time. It is also shown that standard methods may overestimate KT and underestimate PCRN. KT/V and PCRN by these different methods do not correlate with clinical outcomes. However, if V is calculated by Watson's formulae, there is a significant excess of deaths when KT/V is under 0.5 (weekly KT/V under 1.5). Survival curves show that neither initial KT/V nor PCRN predict failure on CAPD.

Female↗

Interactions of cells from peritoneal dialysate with mesothelial cells and fibroblasts in culture.

Peritoneal mesothelial cells and fibroblasts were co-cultured in vitro with peritoneal white blood cells (PWBC) obtained from CAPD patients, after an overnight exchange with 0.5% Dianeal or 2.5% Dianeal. Unstimulated PWBC inhibited proliferation of mesothelial cells and fibroblasts. Upon stimulation with lipoposaccharides (LPS), PWBC from the 0.5% dextrose exchange, enhanced the growth of mesothelial cells and fibroblasts, whereas when stimulated with LPS, PBWC from the 2.5% dextrose exchange increased only proliferation of fibroblasts.

Cell Division↗

CAPD and pancreatitis: no connection.

Autopsy studies have shown that approximately 56% of patients on long-term continuous ambulatory peritoneal dialysis (CAPD) develop various pancreatic abnormalities, such as acute and chronic pancreatitis, fibrosis, and acinar dilatation. This prevalence of anatomical abnormalities is similar to that observed in patients on hemodialysis and higher than that in those with normal renal function. However, clinical acute pancreatitis is an uncommon complication of CAPD (0.9%), and this prevalence is similar to that (1.7%) of patients on hemodialysis. We can attribute acute pancreatitis in CAPD patients to no single factor. Perhaps preexisting anatomical abnormalities of the pancreas make the CAPD patient susceptible to acute pancreatitis when exposed to a variety of physiological and nonphysiological influences. The diagnosis of acute pancreatitis in CAPD patients is difficult, because symptoms and signs are similar to those of dialysis-associated peritonitis. Serum amylase values three times greater than the upper limit of normal and effluent amylase greater than 100 U/L suggest the diagnosis of acute pancreatitis. Serum lipase, isoamylase, and pancreatic secretory trypsin inhibitor are not helpful. In confirming the diagnosis, a computed tomography (CT) scan is more helpful than ultrasound, although it is positive in only 50-60% of cases. One should harbor a high index of suspicion concerning acute pancreatitis if a CAPD patient presenting with suspected peritonitis has either a negative effluent culture or does not respond to antibiotic therapy.

Acute Disease↗

Is total creatinine clearance a good predictor of clinical outcomes in continuous ambulatory peritoneal dialysis?

The measurement of the adequacy of dialysis in continuous ambulatory peritoneal dialysis (CAPD) is controversial. The use of weekly total creatinine clearance (TCC) has been recommended, but not validated. We analyzed data from our recent urea kinetics in a CAPD study to investigate TCC and its relationship to patient outcomes. TCC was measured over 24 hours by adding residual renal and peritoneal creatinine clearance, correcting for 1.73 m2 surface area and converting to a weekly value. Seventy-six patients had 218 measurements, on starting CAPD and then at 6-month intervals, with mean follow-up of 20 months (range 1-57 months). The mean TCC was 73.62 +/- 32.11 L/week. Due mainly to the loss of residual renal function, the TCC decreased with time (r = -0.40, p < 0.0001), from 88.65 L/week initially to 66.11 at one year, 59.84 at two years, and 50.47 at three years. Dialysate-to-plasma creatinine concentration ratios (D/P Cr) increased with time (r = 0.28, p < 0.0001) from 0.62 initially to 0.66 at one year and 0.73 at two years. The TCC correlated significantly with serum levels of creatinine (r = -0.46, p < 0.0001), urea (r = -0.21, p < 0.001), potassium (r = 0.14, p < 0.05), phosphate (r = 0.25, p < 0.001), and hemoglobin (r = 0.16, p < 0.01), but not with serum albumin or with clinical outcomes including technique failure, hospital days, transfusions, peritonitis rate, nerve conduction velocity, or subjective indices of well-being, except for a weak correlation with the fatigue index (r = 0.19, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Creatinine↗