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Biomedical subjects

D G Oreopoulos

Publications and source records attributed to D G Oreopoulos.

At least 109 records · Page 6Linked to original sources

Anabolic steroids and malnutrition in chronic renal failure.

OBJECTIVE: To determine whether anabolic steroids are useful in the management of the malnutrition of chronic renal failure. DATA SOURCE: Original research studies and book chapters about anabolic steroids and their use in uremia and various illnesses associated with malnutrition. We included studies that describe the benefits of anabolic steroids in the treatment of anemia and sexual dysfunction of chronic renal failure. Forty-two such studies were published between 1942 and 1992. RESULTS: Anabolic steroids improve the nutritional status and sexual dysfunction of uremic men. In addition, anabolic steroids have a recognized place in the treatment of the anemia of chronic renal failure. CONCLUSIONS: Based on the findings of noncontrolled studies, one may conclude that anabolic steroids exert a beneficial effect in the malnutrition of renal failure. We believe that their efficacy should be established by controlled studies.

Anabolic Agents↗

Long-term continuous ambulatory peritoneal dialysis in diabetics.

Of 147 diabetic patients with end-stage renal disease who were treated in our CAPD program between 1978 and 1991, 6 men and 1 woman (5 had type II and 2 type I diabetes) with a mean age of 54 (range 21-70) years have been on CAPD for more than five years (mean: 76 mos, range: 65-109 mos) and on peritoneal dialysis (IPD+CAPD) for an average of 85 (range: 67-118) mos. They had a variety of comorbid conditions at the start of CAPD: Retinopathy (5/7), blindness (3/7), hypertension (5/7), peripheral neuropathy (7/7), peripheral vascular disease (3/7), congestive heart failure (3/7), myocardial infarction (1/7), ischemic heart disease (2/7). Two were smokers and five over the age of 65. Peritonitis rate was 1 episode/11.4 pt mos, exit-site infection 1/76.4 pt mos and average hospitalization rate 32.8 days/patient/year. Hypertension was well-controlled with discontinuation of all medications; after initiation of CAPD two of them remained without medications throughout the study but in the rest, medications had to be restarted. As assessed by HbA1c, blood glucose control improved with IP administration of insulin. Residual renal function progressively decreased. None of them developed severe hyperparathyroidism. Peripheral neuropathy remained stable in four and deteriorated in two. Total protein, albumin, cholesterol and triglycerides decreased during the last two years indicating a degree of malnutrition. Our experience with these seven patients suggests that diabetic patients, even the aged and those with many comorbid conditions and complications, can survive for long periods on CAPD.

Comorbidity↗

In vitro influence of lactate on function of peritoneal fibroblasts.

The authors studied the effect of sodium lactate (NaLact) on the function of human peritoneal fibroblasts (F) in vitro. NaLact inhibits the proliferation of fibroblasts in a dose-dependent way: at a concentration of 40 mM, it decreases the growth of these cells by 34%. A similar effect was observed with other solutes (glucose, mannitol, sodium chloride) at identical concentrations, suggesting that the factor responsible for slower growth of the cells was hyperosmolality. When applied to fibroblast monolayers, NaLact (40 mM) increased the synthesis of total proteins by 10%. Exposure of the fibroblasts to NaLact did not increase noncollagen protein production, and the observed increase in total protein synthesis was due to the increased synthesis of collagen. We could not reproduce this effect of lactate on fibroblast collagen synthesis with other osmotic solutes. Our results suggest that dialysis fluid hyperosmolality may be one of the factors responsible for the decrease of the cellular components within the peritoneal interstitium; whereas NaLact is specifically responsible for the increased production of collagen by peritoneal fibroblasts, leading to the deposition of masses of collagen in the extracellular space.

Cell Division↗

Effect of the dialysate effluent from CAPD patients on peritoneal mesothelial cells and fibroblasts.

The authors studied the in vitro effect of overnight "dwelled" dialysate obtained from 5 continuous ambulatory peritoneal dialysis (CAPD) patients on the growth of, and protein synthesis by, peritoneal mesothelial cells and fibroblasts. In each patient, an overnight exchange was performed with Dianeal 2.5% on day 1 and with a solution containing amino acids 1.1% on day 2. Both types of dialysate supported the proliferation of fibroblasts and mesothelial cells, but the amino acid dialysate had a stronger effect on the growth of mesothelial cells than the Dianeal dialysate did. In the presence of either dialysate, synthesis of noncollagen proteins by mesothelial cells and fibroblasts was low. By contrast, the synthesis of collagen was enhanced, and the Dianeal dialysate had a much stronger effect than the amino acid dialysate did. Present results show that, during its intraperitoneal dwell, dialysis fluid within the peritoneal cavity stimulates the generation of bioactive substances which affect the function of peritoneal cells. This reaction is influenced by the composition of the dialysis solution.

Cell Division↗

In vitro study of the effect of osmotic solutes on the interactions between cells from the peritoneum and peritoneal cavity.

OBJECTIVE: To study how the presence of osmotic solutes in medium affects growth of the peritoneal mesothelial cells and fibroblasts and how osmotic solutes influence the production of factors regulating growth of these cells. DESIGN: The proliferation of mesothelial cells and fibroblasts was evaluated by measuring the incorporation of 3H-thymidine into the cells. Cells were exposed to osmotic solutes; the concentration of the latter in the medium was continuously lowered over the time of the experiment to simulate changes of their concentration in the dialysate. The synthesis of factors influencing the proliferation of the mesothelial cells or fibroblasts, by mesothelial cells or fibroblasts themselves, or by peritoneal leukocytes, was tested by the characteristics of the "conditioned" medium. The conditioned medium was produced by exposing standard medium to mesothelial or fibroblasts monolayer or to peritoneal leukocytes over 24 hours; following filtration it was applied to growing test cells for the study of growth factors. RESULTS: The effect of osmotic solutes on the growth of mesothelial cells is less inhibitory when their concentration is gradually lowered over the time of the study, compared to previous findings with a constant concentration. Peritoneal leukocytes produce growth factors for mesothelial cells and fibroblasts. Glucose and amino acids inhibit production of peritoneal leukocyte-derived growth factors for mesothelial cells, while glycerol increases synthesis of such growth factors for fibroblasts. Mesothelial cells produce factors stimulating the proliferation of mesothelial cells and fibroblasts. In the presence of glycerol or amino acids synthesis of mesothelium-derived growth factors for fibroblasts is augmented. Finally, fibroblasts produce factors that inhibit the proliferation of the mesothelial cells, and this effect is potentiated in the presence of amino acids. CONCLUSIONS: Cytotoxicity of the osmotic solutes measured by the inhibition of growth of the mesothelial cells or their increased damage is significantly reduced during in vitro kinetic study when the concentration of these solutes is gradually lowered. Presence of osmotic solutes in the medium affects synthesis of growth factors derived from mesothelium, fibroblasts, or peritoneal leukocytes, which affect the proliferation of mesothelial cells or fibroblasts.

Amino Acids↗

Renal replacement therapies in the elderly: Part 1. Hemodialysis and chronic peritoneal dialysis.

Recent demographic data from the United States and Europe demonstrate that the dialysis population is growing progressively older. In the United States the median age at onset of end-stage renal disease (ESRD) had reached 61 years in 1990, and the fraction of ESRD patients older than 65 years will approach 60% by the year 2000. The primary treatment of geriatric ESRD is center hemodialysis (82% of elderly patients). Chronic peritoneal dialysis in this age group is limited in the United States to less than 10%. Only 2.7% of elderly patients have a functioning transplant. Despite their complex medical and psychosocial conditions, survival and rehabilitation are acceptable in the elderly dialysis patient and these patients tend to be more complaint. Five-year dialysis patient survival rates in the United States are 19% and 10%, respectively, for the 65 to 74 and 75 to 84 age groups compared with 32% and 19%, respectively, for the same age groups in Europe. Five-year survival, particularly in the elderly, is even higher in Japan. Several factors favor the delivery of low doses of hemodialysis in the elderly and discontinuing dialysis is more common in the elderly. Continuous ambulatory peritoneal dialysis is a satisfactory alternative treatment modality for geriatric ESRD. Most studies confirm that survival of elderly patients on continuous ambulatory peritoneal dialysis and hemodialysis is similar. The 1991 United States Renal Data System report showing higher mortality among diabetic continuous ambulatory peritoneal dialysis patients than among hemodialysis patients may reflect selection of such patients, who may have more co-morbid conditions. In special cases, continuous cyclic peritoneal dialysis can be an alternative treatment for elderly ESRD patients.

Age Factors↗

Renal excretion of ascorbic acid: effect of age and sex.

To determine if the lower plasma ascorbic acid concentrations observed in males compared to females, and in the elderly in general, might be due to differences in renal clearances of ascorbic acid, tubular maximum reabsorptions (TmAA) and renal thresholds for ascorbic acid were determined on older (10 male, 10 female, aged 70-86 years) and younger (3 male, 5 female, aged 26-59 years) subjects. The mean TmAA for men was 1.54 +/- 0.29 and for women 1.39 +/- 0.33 mg/minute/100 mL glomerular filtration rate (p > 0.05). The mean renal threshold for men was 1.51 +/- 0.25 and for women 1.26 +/- 0.16 mg/dL (p < 0.02). Neither was affected by age. If differences in TmAA and renal threshold were to explain the lower plasma ascorbic acid concentrations observed in males, both values should have been lower than in females. The ability of women to maintain higher plasma ascorbic acid concentrations than men, and young higher than elderly, cannot be explained by differences in the renal handling of ascorbic acid.

Adult↗

Effect of phosphatidylcholine on the function of human mesothelial cells in vitro.

We tested the hypothesis that phosphatidylcholine (PC) molecules present in the dialysis solution may interact with the mesothelial cell membrane and modify its function. In vitro experiments were performed on human mesothelial cells (HMC) in culture. PC decreased proliferation of HMC when used at concentrations of 200 mg/l and higher. PC was also cytotoxic to HMC as measured by the release of lactate dehydrogenase from their cytosol. Cells exposed to PC had a diminished capacity for taking up 86Rb from medium. PC decreased the fibrinolytic properties of HMC and increased their procoagulant activity. Our results suggest that the positive short-term effect of the addition of PC to the dialysis solution (i.e., an increase in ultrafiltration) may be over-shadowed by its deleterious action on HMC membrane.

Cell Division↗

Toxicity of free radicals to mesothelial cells and peritoneal membrane.

We studied the toxicity of free radicals to human mesothelial cells in vitro and to the peritoneal membrane of rats during peritoneal dialysis. Free radicals cause damage to mesothelial cells as measured by release of cytosolic markers such as 86Rb and lactate dehydrogenase. Vitamin E neutralized the toxic effect of free radicals in vitro. Human mesothelial cells exposed over 6 h to a mixture of essential and nonessential amino acids in medium are more vulnerable to the cytotoxic effect of free radicals than control cells exposed to medium alone. Cells exposed previously to glucose or glycerol are less vulnerable than controls. In rats free radicals generated intraperitoneally by a xanthine-xanthine oxidase system induce changes in peritoneal permeability similar to those observed during peritonitis: loss of ultrafiltration, increased glucose absorption from the dialysate and augmented transperitoneal loss of albumin. In addition lipids in the peritoneum became peroxidated. The addition of vitamin E to the peritoneal fluid with xanthine-xanthine oxidase prevents peroxidation of lipids and the subsequent loss of ultrafiltration. Our results show that free radicals may exert a potentially toxic effect on the peritoneal membrane during peritonitis. In such circumstances the addition of free radical scavenger to the dialysis fluid may preserve intact structure and function of peritoneum.

Animals↗

Serum albumin in patients on continuous ambulatory peritoneal dialysis--predictors and correlations with outcomes.

Serum albumin (SA) is a powerful predictor of patient morbidity and mortality in hemodialysis, but data are limited for continuous ambulatory peritoneal dialysis (CAPD). SA was monitored in 76 new CAPD patients over 222 6-month periods and mean SA was correlated with morbidity and mortality during those periods. The influence of initial SA on duration of technique survival was also investigated. To determine which factors best predict SA, correlations with patient demographics and with 6-month measurements of dialytic dose, protein intake, and peritoneal transport were sought. Mean SA overall was 34.1 +/- 3.3 g/L, and mean initial SA was 33.4 +/- 3.1 g/L. Mean SA was lower in diabetics and in those aged 65 or over. Mean SA tended to increase during the first year on CAPD, and this increase was maintained, except in patients aged 65 or over, where it tended to revert to initial values. SA correlated with hospital days (r = -0.20; P < 0.005), fatigue index (r = -0.20; P < 0.005), nerve conduction (P < 0.001), and a variety of laboratory values, and lower SA was associated with technique failure (P < 0.03) and death (P < 0.07). Initial, as well as ongoing, SA was predictive of technique failure (P < 0.05) and Cox proportional hazards regression showed that this predictive power was independent of age, sex, diabetes, and other factors (P = 0.05). The strongest predictors of low SA by stepwise multiple regression were diabetes, a higher dialysate-to-plasma creatinine equilibration ratio, older age, lower body weight, and shorter time on CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Tidal volume peritoneal dialysis versus intermittent peritoneal dialysis.

In a 12-week crossover study we assessed the effect of tidal volume peritoneal dialysis (TVPD) on serum chemistry, patient well-being, appetite and sleep, blood pressure, and body weight period and compared it with the effect of intermittent peritoneal dialysis (IPD) on these same parameters over a similar period. We used similar volumes of dialysis solutions per exchange and session, and the exchanges were of the same duration in each session. There were 12 patients (6 males, 6 females) with a mean age of 76 years (range 61-88 years), and mean duration of peritoneal dialysis 49 months (range 20-148 months). Five patients started with TVPD and switched to IPD after 3 months; the remaining 7 patients started with IPD and switched to TVPD for the next 3 months. No differences were seen between TVPD and IPD in any of the measured parameters: body weight, appetite, sleep, and well-being by self-assessment, number of transfusions, and complications related to peritoneal dialysis. There were two episodes of peritonitis during the TVPD period and none during the IPD period. Our data indicate that TVPD and IPD are equally effective when applied over similar durations and with similar volumes of dialysis solutions in each session. The improved results with TVPD that others have reported probably can be explained by the use of higher volumes of dialysate.

Aged↗

Enhancement of viability of human peritoneal mesothelial cells with glutathione precursor: L-2-oxothiazolidine-4-carboxylate.

This study tested the effect of L-2-oxothiazolidine-4-carboxylate (procysteine), a precursor of the intracellular cysteine, on the function of human mesothelial cells (HMCs) in in vitro culture. Procysteine stimulated the proliferation of HMCs and decreased the spontaneous death rate of these cells. HMCs pretreated with procysteine were resistant to injury by free radicals. Procysteine also reversed the cytotoxic effects of a mixture of essential and nonessential amino acids on HMCs, such as increased susceptibility to injury by free radicals and inhibition of proliferation.

Amino Acids↗

Clinical associations of glycemic control in diabetics on CAPD.

Diabetic control in 110 diabetics (39 type I and 71 type II), who had been on continuous ambulatory peritoneal dialysis (CAPD) for at least 3 months, was considered good (group G, n = 63) or poor (group P, n = 47) if > 50% or < or = 50% of glucose measurements, respectively, were within 3.3-11.1 mmol/L. Compared to group P, group G had more type I diabetics and fewer type II diabetics; higher serum cholesterol and lower serum creatinine; higher rates of blindness, autonomic neuropathy, congestive heart failure, myocardial infarction, cerebrovascular accidents and extremity gangrene; higher annual rates of peritonitis (1.47 +/- 1.31 vs 0.98 +/- 1.19 episodes/patient-year), exit-site/tunnel infection (0.83 +/- 1.14 vs 0.39 +/- 0.68 episodes/patient-year), and catheter loss (0.81 +/- 0.59 vs 0.39 +/- 0.52 episodes/patient-year); and longer hospitalization (38 +/- 31 vs 14 +/- 15 days yearly). All differences were significant at p = 0.05 or lower. According to life-table analysis, median patient survival was 25 +/- 3 months in group P and 85 +/- 17 months in group G (p < 0.0001). Technique survival was 14 +/- 2 months for group P and 28 +/- 4 months for group G (p < 0.0001). Good diabetic control in diabetics on CAPD is associated with better outcome and constitutes, therefore, a desirable therapeutic goal.

Blood Glucose↗