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Biomedical subjects

S Shaldon

Publications and source records attributed to S Shaldon.

At least 73 records · Page 4Linked to original sources
PubMed1990

Imaging of dialysis-related amyloid (AB-amyloid) deposits with 131I-beta 2-microglobulin.

The diagnosis of dialysis-related amyloid (AB-amyloid) has been based usually on clinical and radiological criteria. Following the discovery that beta 2-microglobulin was the major protein of this amyloid, we isolated and radiolabelled uremic plasma beta 2-microglobulin. After intravenous injection, gamma-camera images of selected joint areas were obtained from 42 patients who were on regular hemodialysis therapy. Positive scans involving the shoulder, hip, knee and carpal regions were found in 13 of 14 patients treated for more than 10 years and 10 of 16 patients treated for 5 to 10 years. Patients treated for less time had negative scans. Specificity was indicated by negative scans in non-amyloid inflammatory lesions in control hemodialysis patients. Up to 48-fold tracer enrichment was detected in excised AB-amyloid containing tissue as compared to amyloid-free tissue. These findings suggest that circulating radiolabelled beta 2-microglobulin is taken up by the amyloid deposits. This method may non-invasively detect tissue infiltrates of amyloid. It may also permit prospective evaluation of the efficacy of prophylactic dialysis strategies which are designed to prevent or delay the onset of this complication of long-term dialysis.

Amyloidosis↗
PubMed1990

Long-term effects of treatment with recombinant human erythropoietin on haemodynamics and tissue oxygenation in patients with renal anaemia.

Regional peripheral vascular resistance, transcutaneous oxygen pressure and blood pressure were studied in seven normotensive, chronically haemodialysed patients with renal anaemia before and after 3 and 12 months of rHuEpo therapy. Haematocrit increased from 21% to 33% within 3 months of commencing therapy, and remained stable throughout the following observation time. Though regional blood flow of the calf was markedly reduced after 3 and 12 months of rHuEpo compared to pretreatment values, transcutaneous oxygen pressure was significantly increased after 3 months and remained constantly elevated after 12 months. Mean arterial blood pressure increased significantly by 7.3 mmHg after 3 months of rHuEpo treatment but did not reach hypertensive values and was no longer different from pretreatment values 12 months after the start of rHuEpo. Results of peripheral haemodynamic studies were compared to those obtained by measurement of central haemodynamics in four further normotensive anaemic patients. In these patients cardiac output decreased, total peripheral vascular resistance increased and blood pressure increased slightly (by 5.5 mmHg) when a haematocrit of 37% was reached after 8 weeks of rHuEpo therapy. These effects were partly reversed when the maintenance haematocrit decreased to 32% (after 16 weeks of rHuEpo). In summary rHuEpo treatment induced a long-term increase of the total and regional peripheral resistance, an increase of blood pressure within the normal range, and a decrease in cardiac output. Despite these changes tissue oxygenation improved.

Adult↗
PubMed1990

Two years experience of daily self-administered subcutaneous erythropoietin.

Recombinant human erythropoietin (EPO) has been used for 4 years in end-stage renal disease patients, administered intravenously 3 times a week. A study was undertaken to determine the optimal way of administration comparing 3 times weekly intravenous EPO to self-administered daily subcutaneous EPO (SADSCEPO). In a first group of 4 patients, we demonstrated that the change from 3 times weekly intravenous EPO to SADSCEPO permitted a dose reduction of 70%. In a second group of 20 patients who started the EPO therapy with the daily subcutaneous route at a median dose of 12 U/kg/day, the hematocrit increased from 20 to 30% in 4 months and remained over 30% in spite of a median dose reduction to 9 U/kg/day. The patients' acceptance of SADSCEPO was good. The mechanism allowing such a dose reduction is unknown. However, the significant reduction in median dosage requirement with the subcutaneous route should allow a greater number of patients to be treated more cost-effectively.

Adult↗
PubMed1990

Chronic haemodialysis with bicarbonate dialysate. Technical and clinical aspects.

Bicarbonate as a physiological buffer should be preferred in haemodialysis treatments. The use of bicarbonate dialysis, however, varies from 30 to 100% in the different industrialised countries. Except for the many advantages using bicarbonate dialysate, there are also clinical pitfalls in the use of the bicarbonate buffer substrate. Furthermore, technical problems can be expected in the use of varying dialysate bicarbonate concentrations, as in the concomitant use of acetate and bicarbonate dialysate in the same dialysis unit. This paper deals with the clinical and technical aspects of bicarbonate dialysis.

Acetates↗
PubMed1990

Renal elimination of beta-2-microglobulin and myoglobin in patients with normal and impaired renal function.

Since the demonstration that beta 2-microglobulin (beta 2M) is an amyloidogenic protein in man, the excretion of this low-molecular-weight protein under conditions with normal and reduced renal function has received increased interest. The renal arteriovenous extraction of beta 2M, polyfructosan (an inulin analogue), and a second low-molecular-weight protein, myoglobin, was measured in vivo in 16 human kidneys with normal renal function/gross morphology and in 22 kidneys with reduced function. In kidneys with normal function, the extraction of beta 2M significantly exceeded that of polyfructosan (0.198 +/- 0.037 vs. 0.182 +/- 0.05; p = 0.04), while that of myoglobin (0.177 +/- 0.068) was not different from that of polyfructosan. In kidneys with reduced function, the extraction of polyfructosan or myoglobin was not significantly altered. In contrast, the beta 2M extraction decreased to 0.110 +/- 0.060 (p less than 0.01 vs. extraction of polyfructosan or myoglobin). This decrease was significantly correlated with the decrease of the endogenous creatinine clearance or the total or unilateral 131I-hippuran clearance. These results indicate that in normal renal function the glomerular filtration of beta 2M may be supplemented by a peritubular mode of removal. The mechanism(s) underlying the selective decrease of beta 2M extraction in kidneys with reduced function remain speculative. However, this decrease will lead to a further augmentation of the retention of beta 2M in renal failure.

Female↗
PubMed1990

Hemodialysis-related induction of beta 2-microglobulin synthesis and release by mononuclear phagocytes.

We have investigated beta 2-microglobulin (beta 2M) synthesis and release by blood leukocytes and isolated mononuclear phagocytes. Since beta 2M was discovered to form amyloid fibrils in patients undergoing long term, chronic hemodialysis and monomeric beta 2M levels in plasma of these patients are highly elevated, and since hemodialysis-related factors that increase beta 2M production are unknown, we evaluated beta 2M production by mononuclear phagocytes under a variety of conditions. We utilized a novel enzyme-lined immunoabsorbant assay to quantitate beta 2M release. Adherence of macrophages onto polystyrene or Cuprophan membranes does not induce beta 2M synthesis or release. In contrast, interaction of macrophages with lipopolysaccharide, gamma-interferon, tumor necrosis factor, or interleukin 1 induces synthesis or release. In contrast, interaction of macrophages with lipopolysaccharide, gamma-interferon, tumor necrosis factor, or interleukin 1 induces synthesis and release of beta 2M, indicating that beta 2M synthesis is increased during macrophage activation. Exposing leukocytes or macrophages to changes in osmotic or oncotic pressure induces a rapid release of beta 2M and interleukin 1 into the cellular medium. These results suggest that during hemodialysis, beta 2M production is more likely to result from endotoxin contamination, or osmotic and oncotic changes, rather than direct interaction of mononuclear phagocytes with cellulosic membranes.

Cell Adhesion↗
PubMed1990

Detection of endotoxin antibody in long-term dialysis patients.

Endotoxins are often seen in dialysate. They are derived from Gram-negative bacteria especially Pseudomonas, E. coli and Serratia. Endotoxins are large-molecular-weight substances with an average molecular weight of 10(8). These large units can be divided into subunits down to a molecular weight of 10,000 which are thought to pass through dialyzer membranes. To investigate this, endotoxin antibody levels were measured in two groups of patients on chronic regular hemodialysis, a low-flux group using cellulosic membrane dialyzers (cuprophan and cuproammonium rayon (CAR) and a high-flux group using synthetic polymer membrane dialyzers (PMMA, EVAL). Using an ELISA based on standard endotoxin antibodies the percentages of patients in the low flux group with endotoxin antibodies were 26.9% with Cuprophan and 25% with CAR, not significantly different from a normal control group. In the PMMA and EVAL groups, it was 53.6% and 68.4% respectively. Back filtration of dialysate into blood is understood as the main reason for the entry of endotoxin in patients treated with high-flux dialyzers.

Antibodies↗
PubMed1989

Is the rise in plasma beta-2-microglobulin seen during hemodialysis meaningful?

Beta 2-Microglobulin (beta 2M) plasma levels and levels of a second low-molecular-weight protein (myoglobin) were studied during a 2- to 4-hour sham dialysis period (no dialysate flow, no weight loss) and during a 4- to 5-hour hemodialysis (HD) with a Cuprophan capillary dialyzer. While no rise of the beta 2M or myoglobin levels occurred during sham dialysis, a rise of 22.1 +/- (SD) 8.5% (beta 2M) or 19.9 +/- 12.1% (myoglobin) was seen during regular HD. The increases of both molecules showed a significant correlation (r = 0.44; p less than 0.03). Both rises could not be completely abolished using correction factors for hemoconcentration. The rises occurred irrespectively of the dialysate buffer. The results suggest that neither the Cuprophan membrane nor the extracorporeal circuit were responsible for the rise of both molecules during HD. It seems more likely that changes of the extracellular volume and extra- to intracellular water shifts are involved and account for the majority of the rise. However, the possibility of minor increase in the extracellular mass of beta 2M or myoglobin cannot be excluded completely.

Adolescent↗
PubMed1989

Comparative study of C5a plasma levels with different hemodialysis membranes using an enzyme-linked immunosorbent assay.

Using a specific and sensitive ELISA for C5a, the present study shows that predialysis levels of C5a in end-stage renal disease patients are not elevated and that all membranes studied (Cuprophan, Hemophan, Gambrane and hydrophilic polysulfone) cause significant increases of C5a plasma levels albeit to different degrees. Higher increases of C5a were accompanied by larger decreases of circulating granulocytes and monocytes. Dialyzers with a newly introduced modified regenerated cellulose membrane, Hemophan, showed lower C5a plasma levels during hemodialysis than Cuprophan. With Hemophan C5a plasma levels were comparable to those with polysulfone membranes.

Adult↗
PubMed1989

Specific imaging of dialysis-related amyloid deposits using 131I-beta-2-microglobulin.

Dialysis-related amyloidosis (DRA), characterized by its association with beta 2-microglobulin (beta 2m), has become a major concern in long-term hemodialysis patients. Hitherto the diagnosis was based on histological examinations of tissue obtained by biopsy or during surgery. In this preliminary study a new noninvasive diagnostic method was developed using the affinity of beta 2m for its derived fibrils. 3 patients on long-term hemodialysis for 10-16 years with biopsy-proven DRA and 1 patient on chronic hemodialysis for only 6 months were examined after intravenous injection of 131I-labelled beta 2m. Specific local accumulation of radioactivity was noted in the DRA patients after 48 h, persisting for further 96 h and corresponding to clinically or radiologically evident sites of amyloid deposition and to several other hitherto unsuspected sites. Examination of an excised amyloid tumor subsequent to in vivo labelling confirmed a highly specific accumulation of radioactivity in the amyloid tissue but not in control tissue. In the patient on chronic hemodialysis for only 6 months, no specific local accumulation was detected even after 1 week. These findings provide in vivo evidence in man that a specific uptake of circulating amyloid precursor molecules into deposits occurs and that this uptake may be used to radiolabel even small tissue infiltrates of amyloid. This method therefore may not only allow an objective, noninvasive detection of DRA but may also be used to obtain new pathophysiologic insights into amyloid formation in man, as well as permitting the evaluation of preventive therapeutic strategies in prospective studies on new patients.

Amyloidosis↗
PubMed1989

Hemodialysis-related induction of beta-2-microglobulin and interleukin-1 synthesis and release by mononuclear phagocytes.

We have investigated beta 2-microglobulin (beta 2M) synthesis and release by blood leukocytes and isolated mononuclear phagocytes. Recent interest in beta 2M has developed since the discovery that this protein forms amyloid fibrils in patients undergoing long-term, chronic hemodialysis and that these patients have greatly elevated levels of monomeric beta 2M in their circulation. Since hemodialysis-related factors that increase beta 2M production are unknown, we evaluated beta 2M production by freshly prepared leukocytes and monocyte-derived macrophages under a variety of conditions. We utilized a novel enzyme-linked immunoabsorbant assay to quantitate beta 2M concentrations, and monitored interleukin-1 and beta 2M synthesis by immunoprecipitation. Incubation of leukocytes with Cuprophan or Hemophan does not increase beta 2M release. Adherence of macrophages onto polystyrene or Cuprophan membranes induces neither interleukin-1 nor beta 2M synthesis or release. In contrast, interaction of macrophages with lipopolysaccharide, gamma-interferon, tumor necrosis factor, or interleukin-1 induces synthesis and release of beta 2 M, indicating that beta 2 M synthesis is increased during macrophage activation. Exposing leukocytes or macrophages to changes in osmotic or oncotic pressure induces a rapid release of beta 2M and interleukin-1 into the cellular medium. These results suggest that during hemodialysis, beta 2M production is more likely to result from endotoxin contamination, or osmotic and oncotic changes, rather than direct interaction of mononuclear phagocytes with Cuprophan membranes.

Cells, Cultured↗