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Biomedical subjects

D G Oreopoulos

Publications and source records attributed to D G Oreopoulos.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

Nutritional assessment of continuous ambulatory peritoneal dialysis patients: an international study.

We examined the nutritional status of 224 patients from six centers in Europe and North America to assess the incidence of protein-energy malnutrition. A "subjective nutritional assessment" was made, using 21 variables derived from history and clinical examination, or anthropometry and biochemistry. Eighteen patients (8%) were severely malnourished, 73 (32.6%) were mildly to moderately malnourished, and 133 (59.4%) did not show evidence for malnutrition. There was a higher incidence of mild to moderate malnutrition in diabetics than in nondiabetics. A statistical analysis identified 12 variables, seven objective and five subjective, that correlated with subjective nutritional assessment. Actual intercenter differences for the incidence of malnutrition were related to patient age, nutritional status at the commencement of continuous ambulatory peritoneal dialysis (CAPD), the length of time on CAPD, and residual renal function. Variables that were most frequently correlated with subjective nutritional assessment and with one another included plasma albumin, mid-arm muscle circumference (MAMC), weight loss, and the clinical judgement of muscle wasting and loss of subcutaneous fat. Loss of residual renal function correlated with muscle wasting and months on CAPD. Our data identified differences between the two sexes. In women there was a trend for more anorexia, greater weight loss from muscle wasting, and a larger decrease in albumin, whereas in men there was a more gradual decrease in nutritional status. Loss of residual renal function contributed to anorexia and symptoms of severe malnutrition.

Adolescent↗
PubMed1991

Lack of correlation between urea kinetic indices and clinical outcomes in CAPD patients.

We examined the predictive value of urea kinetics for patient outcomes in CAPD by measuring dialysis index (DI; a means of quantifying CAPD dose using urea kinetics), KT/V and normalized protein catabolic rate (PCRN) on 222 occasions in 76 new patients at the time of starting CAPD and at subsequent six month intervals. We investigated how these indices altered with time and in relation to each other, and how they correlated with a wide range of subsequent patient outcomes. DI, KT/V and PCRN all tended to decrease with time on CAPD (P less than 0.0004, less than 0.0001 and 0.0005, respectively). DI and KT/V were highly correlated with each other (r = 0.89, P less than 0.0001) and both correlated with PCRN (r = 0.57, P less than 0.0001 and r = 0.60, P less than 0.0001, respectively). DI and KT/V both correlated inversely with subsequent values for serum creatinine (P less than 0.0001), urea (P less than 0.0002), potassium (P less than 0.02) and phosphate (P less than 0.002), and directly with bicarbonate (P less than 0.0001). PCRN correlated inversely with serum creatinine (P less than 0.0002) and directly with urea (P less than 0.0001) and with the number of blood transfusions received (P less than 0.03). None of these indices correlated with levels of hemoglobin, PTH, alkaline phosphatase or albumin, or with nerve conduction velocity or any other subsequent clinical outcomes including death, technique failure, hospital days, peritonitis rate and subjective indices of fatigue, pruritus and insomnia. We conclude that the urea kinetic model is predictive of some biochemical outcomes but not of clinical outcomes in CAPD patients.

Adolescent↗
PubMed1991

Subcutaneous versus intraperitoneal insulin in the management of diabetics on CAPD: a review.

Intraperitoneal and subcutaneous routes of administration for diabetics on CAPD were compared. The comparison included: (1) Control of blood glucose concentration: both methods can provide satisfactory glycemic control for most patients. Changing the method of insulin administration is warranted when one method fails. (2) Effect on plasma insulin levels: intraperitoneal administration can produce a plasma insulin profile similar to the normal profile. This is unusual with subcutaneous administration. Consequences of hyperinsulinemia (hyperlipidemia, hypertension) seem, however, to be similar between the two methods of insulin administration. (3) Effect on peritoneal permeability: permeability characteristics are maintained unchanged, usually, with either method after long-term CAPD. However, insulin is mitogenic in vitro. Theoretically, intraperitoneal insulin could lead to peritoneal fibrosis. (4) Effect on infectious complications of CAPD: a difference in the rate of peritonitis or overall PD catheter-related infections has not been convincingly demonstrated between the two methods of insulin administration. Exit site and tunnel infections with staphylococcus aureus may be more frequent in diabetics receiving insulin subcutaneously. (5) Effect on hepatic structure and function: subcapsular hepatic steatosis was described in diabetics receiving insulin intraperitoneally. The clinical significance of this finding remains to be demonstrated. We conclude that both methods can be applied for insulin administration in diabetics on CAPD. The intraperitoneal method should be tried first in most instances. Prospective studies comparing the two methods are needed.

Diabetes Mellitus, Type 1↗
PubMed1991

Effects of chondroitin sulphate on fluid and solute transport during peritoneal dialysis in rats.

The effect of chondroitin sulphate (CS) on peritoneal fluid and solute transport was studied in rats undergoing peritoneal dialysis. In the presence of CS, net ultrafiltration increased, while absorption of glucose and horseradish peroxidase from the peritoneal cavity decreased. Albumin, used instead of CS, did not modify either fluid or solute transport. In in vitro experiments on isolated rabbit mesentery, CS decreased transmembrane water flow induced by hydrostatic pressure, and its effect was not fully reversed 60 minutes after "wash-out" of this glycosaminoglycan. We postulate that the polyanionic CS molecules are trapped in the peritoneal interstitium, thus decreasing its hydraulic conductivity and permeability, which in turn increases net fluid removal during peritoneal dialysis because of its slower absorption from the peritoneal cavity.

Albumins↗
PubMed1991

Is intraperitoneal tobramycin ototoxic in CAPD patients?

In 40 CAPD patients treated for peritonitis, the authors did a prospective study of ototoxic effects of intraperitoneal tobramycin. They evaluated cochlear function in pure-tone threshold audiograms over a range of frequencies from 250-10,000 Hz, in the speech-reception threshold test and in the speech-discrimination test. These tests were performed within 48 hours of initiation of tobramycin treatment and within 2 or 3 weeks of the drug's discontinuation. With the aminoglycoside doses used in this study, no statistical difference between the mean baseline and mean follow-up hearing levels was seen in these 40 patients. However, according to the standard criteria of ototoxicity, the hearing in 10 of 40 patients (25%) deteriorated after tobramycin, while it improved in seven patients (17.5%). In the remaining 23 (57.5%), hearing remained stable. With respect to the risk factors for ototoxicity such as advanced age, increased duration of treatment, elevated plasma aminoglycoside levels, concomitant treatment with other ototoxic drugs, pre-existing hearing loss, renal dysfunction and hyperthermia, no statistically significant difference was demonstrated between the patients with deteriorated, stable or improved hearing. The results of this study do not confirm that tobramycin given intraperitoneally to CAPD patients produces auditory toxicity. The hearing deterioration observed in 10 patients may be due to synergistic factors. The improvement observed in 7 patients could not be explained.

Audiometry, Pure-Tone↗
PubMed1991

Stimulation of mesothelial cells proliferation by endogenous growth factor(s).

We have attempted to determine whether human mesothelial cells (MC) have the power to influence their own proliferation. A serum-free medium was conditioned with the mesothelial monolayer for 24 hours and then applied to proliferating MC. Conditioned medium increased proliferation rate of MC. When the medium was heated at 60 degrees C for 60 minutes, the growth-promoting activity of the conditioned medium decreased by 50%, suggesting that MC produce at least 2 growth factors, 1 heat-labile and the other heat-stable. When MC were exposed continuously to a medium containing 90 mM glucose growth factor, production was decreased by 35%. However, when the cells were exposed to glucose only on alternate days, growth-factor production was similar to that in the control medium. On the other hand, MC exposed continuously for 10 days to 90 mM of glucose exhibited a weaker response to endogenous growth factor, even in a normotonic medium with low glucose concentration. Our results suggest that MC synthesize factor(s), which stimulate their own proliferation, and that high glucose concentrations interfere with this production and the subsequent action of growth factor.

Cell Division↗