Cerebral edema in uremic animals and humans, as well as an EEG deterioration in humans, has been reported after dialysis. Both are manifestations of the dialysis disequilibrium syndrome (DDS). This study was designed to analyze the changes induced by dialysis in the EEG pattern (spectral analysis), in the cerebral hydration, and ventricular size (computed tomography [CT] of the brain) in a group of 11 stable uremic patients. They volunteered for a randomized crossover study of 4 months each of standard hemodialysis (HD) and hypertonic hemodiafiltration (H HDF). H HDF is a dialysis technique that is shorter and more efficient than HD. An EEG recording, a CT scan of the brain, and blood biochemistry were performed before and after a HD (four hours, blood flow rate 250 mL/min) and a H HDF run (three hours, blood flow rate 400 mL/min). Approximately 6 weeks of stabilization on each treatment were allowed before these studies. No difference was found in the density of seven specific brain structures (base and apical cuts), when comparing pre- v post-HD, pre- v post-H HDF, pre- HD v pre-H HDF, and post-HD v post-H HDF. Furthermore, no difference was evident either in the bicaudate diameter of the lateral ventricles or in the transverse diameter of the third ventricle. In addition, no significant in-between- and within-treatment difference was observed when analyzing the EEG% power (3-7/7-13 Hz) data. In conclusion, this study shows neither a postdialysis change in brain density and ventricular size nor a postdialysis EEG deterioration in a group of stable uremic patients undergoing both a rapid and a standard dialysis treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Comparison of hemodialysis and hypertonic hemodiafiltration on cardiac function [corrected].

This study compared the acute and chronic effects on cardiac function of treatment with hypertonic hemodiafiltration (H HDF) and hemodialysis (HD). Cardiac function was assessed before, during and after a run of H HDF and HD using echocardiography and impedance cardiography in 10 patients in a randomized cross-over sequence, two months after stabilization on each treatment. Blood biochemistry was performed before and after each run. Ejection fraction and fractional shortening were significantly higher before the H HDF run, compared to the HD run, and this difference persisted during and after the treatment runs (both P less than 0.05). There was a corresponding significant difference in the increase of the velocity of circumferential fiber shortening and in the reduction of end systolic diameter during and after H HDF (P less than 0.05). Heart rate, stroke volume, cardiac output, systemic vascular resistance and mean arterial pressure did not differ significantly between the two treatments. Plasma calcium and bicarbonate were significantly higher (P less than 0.03) at the start of H HDF and this difference was enhanced at the end of the run. In conclusion, H HDF compared with HD, is associated with a better myocardial function in both the short and long term treatments. The evidence suggests that this may be due to improved levels of plasma calcium, bicarbonate, and/or the removal of an as yet unidentified myocardial toxin.

Adult↗

PubMed1987

Plasma volume changes induced by hypertonic hemodiafiltration and standard hemodialysis.

We have previously reported that treatment of uremia by hypertonic hemodiafiltration (H-HDF) results in a more stable hemodynamic response as compared to standard hemodialysis (HD). The purpose of this study was to determine if plasma volume (PV) preservation was a significant factor in this response. Nine patients were studied during single treatment sessions of H-HDF and HD. Both sessions were 3 h in duration and the ultrafiltration rate and volume were matched. 10 microCi of 125I human serum albumin were injected 40 min before each session for measurement of PV. Changes in PV during the session were determined from the change in plasma albumin concentration and the hematocrit. The decrease in PV was significantly less during H-HDF. This was associated with a significantly higher plasma sodium and osmolality. The calculated effective osmolality during H-HDF was not only higher than in HD, but showed a significant increase at 2 and 3 h when compared to the baseline level (p less than 0.05). The calculated volume of extravascular mobilization was higher during H-HDF and is probably the mechanism of the PV preservation. In conclusion, this study demonstrates that PV is preserved during H-HDF better than during HD as a result of a more adequate plasma refilling; this appears to be mediated by an increased plasma effective osmolality.

Adult↗

PubMed1987

Plasma volume changes induced by sequential ultrafiltration-hemodialysis and sequential hemodialysis-ultrafiltration.

Isolated ultrafiltration (UF) has been shown to preserve plasma volume (PV) by means of a high plasma refilling rate, mediated by a rapid rise in oncotic pressure. This mechanism contributes to the good tolerance of sequential ultrafiltration-hemodialysis (SUH). This study compared PV changes induced by SUH and sequential hemodialysis-ultrafiltration (SHU). Seven dialysis patients underwent two sets of SUH and SHU, in which 2 h of UF (approximately equal to 3L) respectively preceded or followed 2 h of no-weight-change hemodialysis (ISO HD). VEM (volume of extravascular mobilization), VEM/VUF (percent of plasma refilling rate) and delta PV were calculated by mathematical formulas. Results showed: 1) a high VEM/VUF during the UF period, either before or after ISO HD: 80 and 77% respectively; 2) a significant increase in PV during ISO HD after UF, compared to ISO HD before UF: + 229 ml and + 43 ml, P less than 0.05; 3) VEM/VUF significantly higher during SUH than during SHU: 87 and 80%, P less than 0.01. In conclusion, the decrease in PV was lower in SUH than in SHU (11 vs. 19%, P less than 0.001) because the plasma refilling persisted through the ISO HD period.

Combined Modality Therapy↗

PubMed1986

Complement potentiates the degradation of myelin proteins by plasmin: implications for a mechanism of inflammatory demyelination.

A previous finding, that the basic protein in lyophilized bovine myelin was degraded by macrophage-conditioned media in the presence of plasminogen, suggested that the macrophage-secreted plasminogen activator, along with plasminogen, might have a role in destruction of myelin during inflammatory demyelination. To approximate more closely the conditions expected in vivo, plasmin, or macrophage supernatants plus plasminogen, were incubated with freshly homogenized bovine white matter or freshly isolated myelin, as distinguished from lyophilized myelin. Under these conditions basic protein was not degraded. Phospholipase or lysolecithin potentiated the degradation of basic protein in fresh bovine myelin by plasmin; however, the cultured macrophages did not secrete significant amounts of phospholipase and plasminogen activator simultaneously into the culture media after activation with any of several different agents. Recently myelin was shown to activate complement. After preincubation of fresh myelin with guinea pig serum, as a source of complement, the basic and proteolipid proteins were vulnerable to plasmin or to macrophage-conditioned media plus plasminogen. C3-depleted and C4-deficient sera were not effective, suggesting that these complement components were required for the serum effect. Hypothetically, then, degradation of myelin proteins in the CNS could be initiated by plasminogen activator, secreted by infiltrating macrophages, plus complement and plasminogen, which could enter the CNS through lesions in the blood-brain barrier.

Animals↗

PubMed1986

Solute kinetics in hypertonic hemodiafiltration and standard hemodialysis.

Hemodiafiltration (HDF) is a new dialysis treatment that combines convective and diffusive forces. In order to assess the efficiency of a peculiar model of hypertonic HDF (H HDF), we studied eight uremic patients when they were undergoing five sessions of H HDF of 180 minutes duration and two sessions of standard hemodialysis (HD) of 270 minutes duration with a comparable blood (approximately 400 mL/min) and dialysate flow rate (approximately 520 mL/min). The plasma water clearances (Kw) of small [urea (U), creatinine (C), uric acid (UA), and phosphorus (P)] and middle molecules [netilmicin (N) and inulin (I)] were exceedingly higher in H HDF than in HD; however, because of the different treatment times, U and C removal (R) in HD overcame and UA and P R in HD equalized that in H HDF. The factor time was not sufficient to HD to compensate for the large difference in Kw in the case of I. Additional studies were performed in seven out of the eight patients after two sessions of H HDF and one session of HD. Two significantly higher rebounds were observed when comparing both treatments: for U after HD and for parathyroid hormone (PTH) after H HDF; however, PTH Cx/Cs ratios (ratios of the plasma water concentration of PTH at any postdialysis time to the plasma water concentration of PTH at the start of the run) were not different in both treatments, meaning that there was an increased PTH secretion in the early post H HDF hours in order to compensate for the larger PTH R with H HDF.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood↗

PubMed1986

Netilmicin pharmacokinetics in uremic patients undergoing hemodialysis.

The pharmacokinetics of netilmicin after i.v. administration were studied in 10 adult hemodialyzed patients during and after a dialysis session. The mean interdialysis half-life was 49.6 h, whereas during dialysis this value was reduced to 5.02 h. The mean volume of distribution of netilmicin was about 20% of the total body weight. The dialyzer clearance of netilmicin, measured at 60 and 150 min after the beginning of the session, was about 50 ml/min; this means that 60-65% of the drug may be lost during the 4.5 h standard dialysis. The total body clearance of netilmicin was similar to the dialyzer clearance values, suggesting that the drug is eliminated almost entirely by hemodialysis and that its renal elimination in our patients is negligible. In conclusion, in uremic hemodialyzed patients netilmicin behaves like other aminoglycosides.

Half-Life↗

PubMed1985

Oral aluminum administration to uremic, hyperparathyroid, or vitamin D-supplemented rats.

In the present study, the role of factors was investigated that could possibly lead to changes in plasma and tissue aluminum (A1) concentrations following oral A1 exposure. In chronically uremic rats that received an oral A1 supplementation of 150 mumol/g diet during 4 weeks, a significant increase in mean (+/- SEM) liver A1 content was observed when compared to sham-operated, pair-fed control rats (9.9 +/- 2.0 versus 4.8 +/- 0.65 nmol/g wet weight, p less than 0.02). No such difference was found in non-A1-supplemented rats. Plasma A1 and the A1 content of other organs studied except muscle were not increased in uremic as compared to control animals. In rats with hyperparathyroidism secondary to a calcium-poor diet, mean liver and bone A1 content was significantly decreased when not A1-exposed (2.5 +/- 0.13 and 62 +/- 5.5 nmol/g, respectively) and normal when A1-supplemented (4.7 +/- 0.59 and 120 +/- 23 nmol/g, respectively) as compared to normal control rats without A1 supplementation (5.1 +/- 1.5 and 170 +/- 17 nmol/g, respectively). However, in the hyperparathyroid rats, mean plasma A1 concentration was higher than in control, euparathyroid rats. In rats with exogenous hyperparathyroidism (parathyroid extract) a significant increase in liver A1 content was observed when compared to control rats (8.1 +/- 0.95 versus 5.3 +/- 0.53 nmol/g, p less than 0.05). In A1-supplemented normal rats treated with 1,25(OH)2 vitamin D3 during 4 weeks, liver A1 content was significantly lower than in control rats receiving vehicle solution only (2.9 +/- 0.76 versus 5.7 +/- 0.59 nmol/g, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗

PubMed1985

Effect of oral carnitine supplementation on disturbances of lipid metabolism in the uremic rat.

Carnitine deficiency has recently been incriminated in the pathogenesis of the disturbed lipid metabolism observed in hemodialysis patients. The present study was performed to investigate the effects of L-carnitine administration on the lipid metabolism of rats with experimental chronic renal failure as compared to normal rats. Three groups of rats were studied: the first had induced chronic uremia, the second was sham-operated and pair-fed with the first, and the third was sham-operated and fed ad libitum. Serum triglycerides were significantly higher in uremic rats than in control animals of both groups. In addition to triglycerides, serum total cholesterol and phospholipids were also increased in uremic rats. The fractional clearance rate of Intralipid [K2(%)] was decreased in uremic as compared to control animals. The in vivo oxidation of radiolabeled palmitate was lower in uremic than in ad libitum-fed control animals but not lower than in pair-fed control rats. The daily oral administration of L-carnitine to uremic rats was associated with stable serum triglycerides. On the contrary, serum triglycerides increased significantly in the untreated uremic rats over the same period of time. Serum total cholesterol and phospholipids remained similar in the presence and the absence of L-carnitine treatment. The intravenous fat tolerance test of carnitine-supplemented uremic rats improved slightly, although not significantly, when compared to that of untreated uremic rats. In conclusion, oral L-carnitine supplementation in chronically uremic rats had only modest or no effects on several plasma lipid parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1985

Pharmacokinetics of netilmicin in hypertonic hemodiafiltration and standard hemodialysis.

Recently, we developed a peculiar model of hemodiafiltration (HDF), in which a conventional acetate hemodialysis (HD) is combined with a high flux dialyzer, a high ultrafiltration flow rate and a postdilution hypertonic reinfusion (H HDF). The pharmacokinetics of netilmicin (N), a relatively new aminoglycoside, were evaluated during 5 sessions of H HDF of 180 min and 2 sessions of HD of 270 min in the same 8 patients with a comparable blood (approximately 400 ml/min) and dialysate flow rate (approximately 520 ml/min). Additional studies were performed in 7 out of the 8 patients after 2 sessions of H HDF and one session of HD. N clearance, calculated both as plasma water and total body clearance, was so exceedingly higher during H HDF than during HD, that the amount of drug removed by H HDF in 180 min was still significantly higher than that removed by HD in 270 min. Consequently, the N half-life during HD was about 5 h, whereas during H HDF it was less than 2.5 h, approaching that reported in normal subjects. N half-life out of dialysis treatments was about 55 h. In conclusion, N pharmacokinetics are strikingly different between H HDF and HD, with N clearance during H HDF about the double of that during HD. The implications of this study are: a different dosage adjustment of aminoglycosides is needed for patients routinely treated by HDF; HDF may be a very effective treatment for the overdose of many drugs.

Adult↗

PubMed1984

Total parathyroidectomy and delayed parathyroid autotransplantation using a simplified cryopreservation technique: human and animal studies.

Following earlier studies using a simplified cryopreservation method in rats, we report the successful use of this technique in a hemodialysis patient who had previously undergone total parathyroidectomy. In additional studies, parathyroid glands from rats were conserved by this rapid freezing procedure after total parathyroidectomy. Six weeks after parathyroid autotransplantation the animals were submitted to a low-calcium diet and their parathyroid gland function compared to that of rats that had previously undergone sham operation, immediate autotransplantation, or delayed autotransplantation using the classical cryopreservation method. With both cryopreservation techniques, plasma calcium, phosphorus, and 1,25 (OH)2 vitamin D concentrations after low-calcium diet were similar although results were less satisfactory than with immediate autotransplantation or after sham operation. We suggest that this simplified cryopreservation technique, developed in rats, yields functioning parathyroid gland tissue and can be successfully used in the human.

Adult↗

PubMed1983

One-hour and half, high-surface-area haemodiafiltration: a feasibility study.

In order to explore the limitations of further shortening of dialysis time, six uraemic patients underwent three different dialysis treatments: haemodiafiltration (HDF) of 180 min with a polyacrylonitrile membrane (1 m2); standard haemodialysis (SH) of 270 min with a cuprophan membrane (1 m2); 90 min, 2 m2 haemodiafiltration (H HDF) with two RP6 in series, dialysate coursed through the two dialysers in parallel and postdilution reinjection of 220 mEq/L of Na+ and 100 mEq/L of bicarbonate after each dialyser. Clearances were extremely more elevated in H HDF than in SH; urea extraction index was significantly higher in SH, but inulin extraction index was significantly lesser in SH than in H HDF.

Blood Flow Velocity↗

PubMed1982

Morphological and biochemical variations in the skin of Rana esculenta during the annual cycle.

Explore the source record for details and available documents.

Animals↗

PubMed1982

Parathyroid function and lipid metabolism in the rat.

The present investigation in experimental animals was designed to obtain further insight into the possible role of parathyroid hormone (PTH) in lipid metabolism. An endogenous hyperparathyroid state was induced in rats by a calcium-poor diet. This type of hyperparathyroidism was associated with a significant increase in serum cholesterol and triglyceride concentrations, a significant decrease in the serum clearance rate of intravenously infused Intralipid and a significant increase in hepatic tissue triglyceride content as compared to the values obtained in control animals. An exogenous type of hyperparathyroidism (parathyroid extract injections) was also accompanied by a slight increase in serum cholesterol and triglyceride concentrations as well as a decrease in plasma postheparin lipolytic activity (PHLA), but the changes did not reach the level of statistical significance. In the aparathyroid state, a significant decrease in serum cholesterol and triglyceride concentrations and a significant increase in plasma PHLA were observed as compared to control rats. In additional studies, it could be demonstrated that the endogenous hyperparathyroid state was not associated with increased intestinal absorption of [3H]triolein as compared to control animals. Furthermore, the hepatic triglyceride secretion rate in these hyperparathyroid rats was significantly lower than in normal rats. In conclusion, hyperparathyroidism induces an increase in serum cholesterol and triglyceride concentrations, the latter being due to decreased peripheral removal. The aparathyroid state induces opposite changes. Thus, normal parathyroid function is required for normal lipid metabolism in the rat.

Animals↗