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Biomedical subjects

S Shaldon

Publications and source records attributed to S Shaldon.

At least 37 records · Page 2Linked to original sources
PubMed1997

Continuous administration of intravenous iron during haemodialysis.

A simple, safe and potentially cost effective method of giving intravenous iron to patients receiving regular haemodialysis therapy is described. The heparin and iron are mixed in normal saline and given as a continuous infusion via the syringe pump present on the modern dialysis machine. No pharmacological incompatibility was observed between iron polymaltose and Heparin Choay or Heparin Roche. No adverse reactions attributable to i.v. iron were observed in over 400 patients and more than 30,000 dialyses.

Anaphylaxis↗
PubMed1997

Detection of peptidoglycan and endotoxin in dialysate, using silkworm larvae plasma and limulus amebocyte lysate methods.

Silkworm larvae plasma (SLP) reagent is activated by peptidoglycan (PG), a fragment of both the gram-positive and gram-negative bacterial cell wall, as well as beta-glucan (BG), a component of fungi. It is possible to measure contamination of gram-positive bacteria quantitatively by combining the conventional limulus amebocyte lysate (LAL) and PG measurement methods. Therefore, a more highly accurate analysis of dialysate can be made using both SLP and LAL methods to detect endotoxin (ET) and/or PG contamination. We studied the effects of contaminated dialysate on human peripheral blood mononuclear cells (PBMC) by producing various cytokines in vitro. Muramyl dipeptide (MDP) was used as the biologically active minimum constituent of PG. A total of 54 dialysate samples were obtained under sterile conditions from 4 sites: (1) reverse osmosis water unit; (2) proportioning unit; (3) multiple dialysate preparation console, and (4) personal dialysate preparation console, at 9 dialysis facilities. To detect bacterial contamination, the samples were measured with LAL(C), LAL(G) and SLP methods. PBMC were collected from 10 healthy controls and from 10 hemodialysis patients and cultured for 24 h with ET, MDP, ET + MDP and contaminated dialysate. IL-1 receptor antagonist (IL-1Ra), IL-1 beta and TNF-alpha in the culture medium supernatants were measured using the ELISA method. PG was not detected in dialysate from sites 1 or 2. However, dialysate from the inlet of the dialyzer at the bedside monitor of the central supply and personal console showed 4.1 +/- 6.1 ng/ml for site 3 (in 7 of 18 samples) and 3.3 +/- 4.6 ng/ml for site 4 (in 3 of 18 samples). Contamination by PG alone and complex contamination by PG and ET were also detected. Furthermore, IL-1Ra, IL-1 beta and TNF-alpha production by PBMC increased in accordance with the concentrations of MDP. Cytokine production was enhanced 5-10 times more where MDP and ET coexisted than where either MDP or ET existed alone, showing the synergic effects of MDP and ET. Based on these results, there is a high possibility that PG may also be a pyrogen in the dialysate prior to this study. ET had been considered the only pyrogen in dialysate. Therefore, it is essential to recognize the existence of both ET and PG in investigating dialysate contamination.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1997

Management of iron deficiency in renal anemia: guidelines for the optimal therapeutic approach in erythropoietin-treated patients.

Much progress has been made in recent years in the management of anemia associated with chronic and renal failure with recombinant human erythropoietin (r-Hu EPO). However, there remains much debate surrounding the diagnosis and treatment of iron deficiency. To ensure that full benefit from erythropoietin therapy is received, most patients require iron supplement during treatment. There are, however, few guidelines for the use of iron therapy. Iron deficiency results in an inadequate response to r-Hu EPO and is the main cause of resistance to this treatment. Oral iron therapy is of limited value in patients receiving r-Hu EPO. Thus, intravenous iron supplementation should be administered only in patients who do not tolerate available intravenous iron preparations or who are on continuous ambulatory peritoneal dialysis with no evidence of functional iron deficiency. This article provides guidelines for the diagnosis of absolute or functional iron deficiency in patients with renal anemia and suggests treatment schedules for intravenous iron supplementation. We hope that all dialysis patients will be able on this basis to achieve a satisfactory iron status and benefit fully from r-Hu EPO therapy.

Anemia↗
PubMed1996

Bacterial challenge of NISSHO ultrafilter ETF 609: results of in vitro testing.

In hemodialysis, a certain degree of bacterial contamination on the dialysate side is a regular finding. Concern has been growing that this contamination may lead to a chronic inflammatory response in the patient. Ultrafiltration of dialysate can be used to reduce bacterial content and levels of cytokine-inducing substances upstream of the patient's dialyzer. The aim of this study was to test in vitro the rejection capacity of a polysulfone hollow-fiber ultrafilter (ETF 609, NISSHO Co., Osaka, Japan) challenged with bacterial filtrates derived from Pseudomonas aeruginosa PA103. Results showed a reduction of interleukin-1 beta-inducing activity (measured on peripheral blood mononuclear cells) from 5,035 +/- 394 pg/ml prefilter to nondetectable levels postfilter and endotoxin levels (limulus amebocyte lysate assay) of 4,167 +/- 1,079 versus 12 +/- 2 pg/ml, respectively. In conclusion, ultrafiltration of dialysate with the polysulfone ultrafilter ETF 609 leads to a potent reduction of cytokine-inducing activity.

Endotoxins↗
PubMed1996

Retention of cytokine-inducing substances inside high-flux dialyzers.

Reprocessing of dialyzers is often performed with nonsterile solutions possibly contaminated with bacterial-derived cytokine-inducing substances. We investigated the retention of cytokine-inducing substances inside the dialyzer during reprocessing in a closed loop in vitro hemodialysis system using a polyamide high flux membrane. After the first in vitro circulation of human whole blood, rinse of the blood compartment (BC) and reverse ultrafiltration (RUF) was performed with either cytokine-inducing substance-free saline or saline contaminated with filtrates from Pseudomonas cultures (6 ng/ml LAL-reactive material); subsequently, dialyzers were stored in 2% formaldehyde. Dialyzers were rinsed with approximately 15 liters pyrogen-free saline before the second circulation using blood from the same donor; the effluates were free of cytokine-inducing substances and formaldehyde. Before and after the blood circulations, peripheral blood mononuclear cells (PBMC) were separated and total production of IL-1 alpha and IL-1 beta was determined after overnight incubation. In noncirculated PBMC as well as in PBMC separated after whole blood circulation with pyrogen-free processed dialyzers, production of IL-1 beta was not detectable. After contaminated rinse of the BC, production of IL-1 beta could be observed (1,600 +/- 1,100 pg/ml, mean +/- SEM). When pyrogen-free RUF was performed after contaminated BC rinse, IL-1 beta production averaged 163 +/- 92 pg/ml when using reused dialyzers, but 1,820 +/- 880 pg/ml when using new dialyzers. After reuse with pyrogen-free BC-rinse and contaminated RUF no IL-1 beta synthesis was observed; however, when pyrogen-free BC-rinse and contaminated RUF was applied to new dialyzers, IL-1 beta synthesis averaged 1,620 +/- 1,200 pg/ml. We conclude that cytokine-inducing substances are retained inside the dialyzer, probably by adsorption to the membrane as well as to the protein layer covering the membrane and are still biologically active after sterilisation. Cytokine-inducing substances adsorbed to the protein layer can be partially removed by RUF. Finally, the protein layer on the membrane appears to reduce the convective transfer of cytokine-inducing substances from the dialysate into the blood compartment.

Bacteriological Techniques↗
PubMed1996

Induction of interleukin-1 and interleukin-1 receptor antagonist during contaminated in-vitro dialysis with whole blood.

BACKGROUND: Previous studies on the permeability of cellulosic and synthetic dialysers for bacterial-derived cytokine-inducing substances gave conflicting results. We tried to study this issue as close to the in-vivo situation as possible. METHODS: An in-vitro dialysis circuit with whole human blood present in the blood compartment of cuprophane (Cup), polysulphone (PS), and polyamide (PA) dialysers was employed; sterile filtrates derived from Pseudomonas aeruginosa cultures were added to the dialysate. We studied the induction of interleukin-1 beta (IL-1 beta) by plasma samples taken from the blood compartment as well as the induction of IL-1 beta and interleukin-1 receptor antagonist (IL-1Ra) in mononuclear cells separated from whole blood after circulation by radioimmunoassay and polymerase chain reaction. RESULTS: Plasma samples from the blood side of all dialysers induced IL-1 beta from non-circulated mononuclear cells after addition of pseudomonas filtrates to the dialysate; the maximal amount of IL-1 beta induced by samples from the blood compartment was 4.8 +/- 1.2 ng/ml for Cup, 1.9 +/- 0.5 ng/ml for PS, and 2.0 +/- 0.6 ng/ml for PA. Mononuclear cells separated after contaminated dialysis will all types of dialysers expressed increased mRNA levels for IL-1 beta and IL-1Ra. Production of IL-1Ra by cells separated after contaminated dialysis was determined after Cup and PS dialysis; there was increased production of IL-1Ra by these cells (Cup, 10.3 +/- 4.2; PS, 7.3 +/- 2.5 ng/ml) compared to cells separated after sterile dialysis (Cup, 5.6 +/- 2.1, P < 0.05; PS, 4.5 +/- 1.1 ng/ml, n.s.) or from non-circulated blood (Cup experiments, 4.7 +/- 1.5, P < 0.05; PS experiments, 4.1 +/- 1.2 ng/ml, n.s.). CONCLUSIONS: These data suggest penetration of cytokine-inducing substances through both cellulosic and synthetic dialysers. Differences between dialysers may exist regarding extent and time course of penetration. The detection of cytokine mRNA as well as the measurement of IL-1Ra synthesis is a more sensitive marker for the transfer of cytokine-inducing substances through dialyser membranes than the measurement of IL-1 beta protein synthesis.

Base Sequence↗
PubMed1995

Impaired endotoxin-induced interleukin-1 beta secretion, not total production, of mononuclear cells from ESRD patients.

Lipopolysaccharide (LPS)-induced interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) production and secretion from peripheral blood mononuclear cells (PBMC) were determined in a longitudinal study with repeated measurements in PBMC from patients with chronic uremia not on hemodialysis (N = 8), end-stage renal disease (ESRD) patients (N = 8), and healthy controls (N = 7). ESRD patients were studied while using low-flux Cuprophan dialyzers and again using high-flux AN 69 dialyzers. Total (cell-associated plus secreted) LPS-induced IL-1 beta production was enhanced in uremic patients, but similar to controls in ESRD patients on Cuprophan. In contrast, LPS-induced IL-1 beta secretion (secreted amounts in % of total production) was similar to controls in uremic patients, but significantly reduced in ESRD patients on Cuprophan (P < 0.01). During AN 69 hemodialysis, LPS-induced total IL-1 beta production remained unchanged but IL-1 beta secretion increased significantly (P < 0.05) compared to Cuprophan dialysis. Increased IL-1 beta secretion coincided with a suppression in PGE2 synthesis (P < 0.02). Similarly, blockade of endogenous PGE2 by indomethacin increased LPS-induced IL-1 beta secretion (P < 0.01) but did not enhance total IL-1 beta production in PBMC from controls and patients on Cuprophan hemodialysis. Neither total production nor secretion of TNF alpha was different comparing the three study groups. We conclude that LPS-induced IL-1 beta secretion, but not total production, is impaired in PBMC from ESRD patients on long-term Cuprophan hemodialysis. This functional change in the PBMC response is specific for IL-1 beta, not due to uremia per se but hemodialysis-dependent and reversible. Hemodialysis with AN 69 suppresses endogenous PGE2 synthesis in PBMC which is associated with increased LPS-induced IL-1 beta secretion in the presence of unchanged total IL-1 beta production. We speculate that PGE2 could inactivate the IL-1 beta converting enzyme which is essential for processing and secretion of mature IL-1 beta.

Adult↗