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Biomedical subjects

J Zingraff

Publications and source records attributed to J Zingraff.

At least 55 records · Page 3Linked to original sources
PubMed1991

Can the nephrologist prevent dialysis-related amyloidosis?

The pathogenesis of dialysis-related amyloidosis is still poorly understood. Therefore, preventive measures can be proposed at present only on the basis of retrospective studies and hypothetical considerations. Two main solutions may be recommended, namely an effective dialytic removal of beta 2-microglobulin (beta 2-M), which is the protein precursor of dialysis amyloid, and the avoidance of bioincompatibility-associated phenomena such as those induced by dialysis membranes and endotoxins. Promising new imaging techniques such as computed tomography (CT) scan, nuclear magnetic resonance (NMR), and scintigraphy with specific tracers for amyloid may be helpful to evaluate the long-term results of different treatment schedules, including various strategies of renal replacement therapy.

Amyloidosis↗
PubMed1991

Elevated circulating levels of interleukin-6 in patients with chronic renal failure.

In a previous study, we demonstrated the presence of circulating interleukin-1 (IL-1) in long-term dialyzed patients and that of tumor necrosis factor alpha (TNF alpha) in both long-term and not yet dialyzed uremic patients. In the present study, we attempted to determine the respective influence of hemodialysis (HD) and uremia on the plasma level of interleukin-6 (IL-6), which shares several biological properties with IL-1 and TNF alpha, including the induction of the acute phase response of the inflammatory process. Forty-eight patients with end-stage renal failure, including 32 long-term HD patients and 16 chronic uremic patients undergoing their first dialysis session, were tested for plasma IL-6 using both biological and immunoreactive assays. Plasma IL-6 activity was significantly increased in patients with chronic renal failure (P less than 0.001) compared to its level in normal individuals. No difference was observed, however, between long-term and not yet dialyzed patients. In the patients with the most pronounced IL-6 activity, immunoreactive IL-6 levels between 60 and 150 pg/ml were detected. A monoclonal antibody (mAb) against human IL-6 inhibited the activity of plasma in the IL-6 bioassay, and a close correlation existed between the biological activity of IL-6 and its immunoreactive level. No change in plasma IL-6 was detected during the course of the first dialysis as well as subsequent sessions. Likewise, no influence of the nature (cellulosic or synthetic polyacrilonitrile) of the dialysis membrane equipping the dialyzer was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Assay↗
PubMed1991

Influence of first and long-term dialysis on uraemia-associated increased basal production of interleukin-1 and tumour necrosis factor alpha by circulating monocytes.

In a previous study we demonstrated the presence of circulating interleukin-1 (IL-1) in long-term haemodialysis patients and of tumour necrosis factor alpha (TNF alpha) in both long-term haemodialysis and not-yet-dialysed uraemic patients. The present report investigates the spontaneous capacity of monocytes to produce and secrete these two cytokines in 35 long-term haemodialysis patients and 36 uraemic patients undergoing their first dialysis session. Predialytic cell-associated IL-1 concentrations in freshly isolated monocytes were significantly increased both in long-term haemodialysis and first-dialysis uraemic patients compared to normal individuals. In both groups in comparison to normal individuals, although intracellular TNF alpha could not be detected in freshly isolated monocytes, both extracellular IL-1 and TNF alpha concentrations were greatly increased after 20 h of in vitro culture of monocytes in the absence of exogenous stimulation and in serum-free conditions. However, long-term haemodialysis patients showed higher values of secreted IL-1 than not-yet dialysed uraemic patients. During a single dialysis session a significant increase in both cell-associated and secreted IL-1 but not TNF alpha was observed in long-term haemodialysis patients. In contrast, no change in the concentration of either cytokine could be detected at the end of the first dialysis session in uraemic patients. Our findings strongly suggest that factors related to uraemia could be a sufficient signal to initiate intracellular IL-1 protein synthesis and TNF alpha release by monocytes, but that greater IL-1 release could be stimulated during the periodic haemodialysis procedure.

Cells, Cultured↗
PubMed1991

Serum erythropoietin and erythropoiesis in primary and secondary hyperparathyroidism: effect of parathyroidectomy.

Primary as well as secondary hyperparathyroidism may be associated with anemia, and parathyroidectomy (PTx) may improve or even heal it. The precise link between the two conditions is still matter of discussion. The purpose of the present study was to investigate possible effects of PTx on serum immunoreactive erythropoietin (iEPO) in secondary (group I, n = 23), and primary (group II, n = 16) hyperparathyroidism patients, and in 3 patients undergoing cervicotomy for thyroid mass removal (group III). In group I patients, circulating iEPO levels rose from 23.1 +/- 4.8 mU/ml before PTx to 28.2 +/- 5.0 and 245 +/- 125 mU/ml (mean +/- SEM) at day 7 (p = NS) and 14 after PTx (p less than 0.003), respectively. Reticulocyte count increased 2 weeks after PTx: from 61,000 +/- 13,317 to 86,533 +/- 13,462/mm3 (p less than 0.05, n = 23). In 4 of these patients serum iEPO levels could be measured again 12-24 months after PTx. They were slightly higher than those determined before PTx: 37.0 +/- 8.4 versus 31.8 +/- 13.5 mU/ml. Their hematocrits were also higher than before PTx: 12.8 +/- 0.9 versus 11.0 +/- 0.9 g/dl. In group II patients, serum iEPO levels remained unchanged after PTx: 17.5 +/- 2.0 mU/ml before PTx and 20.0 +/- 3.0 mU/ml 14 days PTx. The reticulocyte count, however, increased significantly 2 weeks after PTx: from 25,103 +/- 3,000 to 40,827 +/- 4,080/mm3 (p less than 0.01). In group III patients, serum iEPO, reticulocyte count, and hemoglobin remained stable after surgery. Since all group I patients had received vitamin D supplementation after PTx, we studied an additional group of 14 chronic dialysis patients (group IV) who received either calcitriol (1 micrograms/day, n = 7) or placebo (n = 7) during 14 days. The patients on calcitriol treatment, but not those on placebo, had a significant decrease of serum iEPO: 18.6 +/- 4.9 versus 16.0 +/- 4.2 mU/ml (p less than 0.03). In conclusion, PTx led to a striking increase of serum iEPO and blood reticulocytes in uremic patients with secondary hyperparathyroidism, and an increase of reticulocyte count, but not of iEPO, in patients with primary hyperparathyroidism. Marked changes of circulating PTH, extra-or intracellular calcium and phosphorus concentrations as well as of tissue sensitivity to EPO after PTx could all be responsible. In contrast, the surgical procedure and the therapeutic increase in plasma calcitriol do not appear to be involved.

Calcitriol↗
PubMed1991

[The future of hemodialysis in the adult].

By the year 2000, the perspectives for hemodialysis performed in adults will be oriented towards facilitation of the practice of hemodialysis as a better control of clinical symptoms observed in end stage renal failure treated by hemodialysis. Blood access is the main problem which remains to be solved. The authors describe the advantages and disadvantages of the methods presently used and give the "state of the art" of "blood access" prosthesis. Almost all symptoms encountered in renal failure patients treated by hemodialysis can be efficiently treated. Hypotensive drugs usually reduce hypertension which resists adequate treatment by hemodialysis. Most of the symptoms of osteodystrophy can be avoided by adequate diet associated with the prescription of vitamin D analogs. Nevertheless, the prolongation of hemodialysis treatment duration over 7 years has led to the apparition of destructive arthropathies which are very painful and handicapping. They are related to amyloid deposit of beta 2-microglobulins. Progress in hemodialysis technics and a better control of uremic symptoms allow application of this treatment at all ages of life. The authors examine specific problems concerning school-aged teenagers and aged persons. They show that results already achieved allow a daily treatment of these patients. This is a first step for the generalisation of this procedure to all patients and its advantages are described. Improvement of hemodialysis technics for the year 2000, as can be expected, mainly depends upon progress in knowledge of biocompatibility parameters between materials used in the artificial kidney and patients tissues, mainly blood vessels.

Adult↗
PubMed1990

Pseudotumor of the craniocervical junction during long-term hemodialysis.

A systematic study of the upper cervical spine was performed using magnetic resonance imaging in 25 patients (15 men and 10 women) who had been undergoing hemodialysis for more than 10 years. Seven pseudotumors of the periodontoid soft tissue were disclosed, which were similar to the pannus recently described in rheumatoid arthritis. Bone cystic radiolucencies were observed in association with these pseudotumors in 5 patients. The radiolucencies were located in the atlas (1 in the lateral mass and 1 in the anterior branch) and in the axis (3 in the odontoid process and 1 in the vertebral body). No horizontal or vertical atlantoaxial subluxation was demonstrated. These features were observed only in patients who had amyloid arthropathy. They could be a frequent, yet thus far little-recognized, feature of beta 2-microglobulin amyloidosis.

Adolescent↗
PubMed1990

Influence of uremia and hemodialysis on circulating interleukin-1 and tumor necrosis factor alpha.

Interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) were determined in the plasma of long-term hemodialysis (HD) patients and uremic (UR) patients undergoing their first dialysis session using either cellulosic (CUP) or synthetic (PAN-AN 69) membrane-equipped dialyzers. In long-term HD patients, plasma IL-1 and TNF alpha levels were significantly increased compared to their levels in normal subjects. During a single dialysis session, a significant increase in IL-1 but not in TNF alpha was observed. In not yet dialyzed UR patients, IL-1 plasma levels did not differ from those observed in normal subjects. By contrast, TNF alpha was found significantly increased although less than in long-term HD patients. During the first dialysis session, no significant increase was observed in the levels of either monokine. Lastly, regardless of the group of patients, no significant influence of the dialysis membrane could be detected, suggesting that the observed changes are not exclusively secondary to the activation of complement. Altogether, these results suggest that the passage of the blood through the extracorporeal dialysis circuit triggers the secretion of IL-1 and further exacerbates that of TNF alpha by monocytes. The presence of increased TNF alpha in the plasma of first-dialysis UR patients suggests that factors unrelated to dialysis contribute to the activation of monocytes in these patients. Lastly, the concomitant presence of IL-1 and TNF alpha in the plasma of long-term HD patients could be responsible for some of the clinical features observed in these patients, and provides strong evidence favoring the concept that HD can be assimilated to a recurrent acute-phase inflammatory response.

Acrylic Resins↗
PubMed1990

Aluminium intoxication in the rat induces partial resistance to the effect of recombinant human erythropoietin.

Anaemia is a major complication of chronic renal failure. It is mainly due to a decrease in the production of erythropoietin and at present it can be corrected by recombinant human erythropoietin (rHuEpo). The question has arisen whether aluminium overload, which is frequently observed in uraemic patients, could exert a resistance to the effect of rHuEpo. To answer this question, we submitted two series of rats with two groups in each to an experimental aluminium intoxication. Group II rats received repeated i.p. injections of aluminium, whereas group I (control) rats were given vehicle solution alone. Subsequently, all rats were treated with identical s.c. doses of rHuEpo (100 IU/kg body-weight twice weekly). In the first series, rats were fed ad libitum whereas in the second, rats were pair-fed and received iron supplementation. In the first series, group I rats had an increase of mean haemoglobin in response to rHuEpo: 15.6 +/- 0.3 vs 19.8 +/- 0.3 g/dl, P less than 0.001. In contrast, group II rats had a decrease: 15.1 +/- 0.2 vs 10.1 +/- 0.8 g/dl, P less than 0.001. However, compared to group I rats, group II rats did not gain body-weight and their plasma iron concentration was less. In the second series, mean haemoglobin concentration of group I rats increased from 15.1 +/- 0.2 to 18.9 +/- 0.3 g/dl (P less than 0.001) in response to rHuEpo.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1990

Beta 2-microglobulin amyloidosis: a sternoclavicular joint biopsy study in hemodialysis patients.

The incidence of beta 2-microglobulin deposits appears to increase with time on dialysis. However, the precise prevalence of the disease is not known at present because adequate, noninvasive diagnostic procedures are still lacking. We performed systematic synovial biopsies of the sternoclavicular joint during surgical parathyroidectomy in 22 chronic hemodialysis patients with severe hyperparathyroidism. Nine of the patients proved to have beta 2-microglobulin amyloid deposits as demonstrated by Congo red staining and by immunofluorescence. They had undergone dialysis for longer time periods (12.6 vs 8.5 years, p less than 0.02) and tended to be older than the 13 amyloid-negative patients. They also had a significantly higher body aluminum overload, as demonstrated by a higher increase of plasma aluminum after desferrioxamine infusion. Finally, the presence of Congo-red-positive deposits correlated well with clinical and x-ray findings suggestive of dialysis amyloidosis.

Amyloidosis↗
PubMed1989

Short-term effects of parathyroidectomy on plasma biochemistry in chronic uremia.

Parathyroidectomy (PTx) is indicated in hemodialysis (HD) patients who have severe osteitis fibrosa unresponsive to vitamin D therapy or in whom the latter treatment is contraindicated. Immediately after PTx, plasma immunoreactive parathyroid hormone, calcium and phosphorus concentrations decline abruptly. However, little is known in such patients about the short-term effects of PTx on plasma alkaline phosphatase (AP) activity and plasma aluminum (Al) levels. The present, preliminary study was performed to determine such parameters in 37 HD patients, and to correlate them with data of bone histology. Mean plasma AP activity started to increase after PTx from day 4 onwards. Thus, AP values significantly higher than pre-PTx values were observed at day 7 and 14 (415 +/- 54 vs. 619 +/- 77 and 749 +/- 83 IU/liter, means +/- SEM; N = 37; P less than 0.05 and 0.001, respectively). This increase, in the absence of changes in liver function, was mainly due to the bone-specific iso-AP. Moreover, the degree of increase in plasma AP activity was higher in the subgroup with negative (group I, 21 patients) than in that with positive bone Al staining (group II, 16 patients). However, plasma osteocalcin (BGP) did not change after PTx (N = 8). Basal plasma Al levels were significantly higher in group II both before and two weeks after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1989

Utilization of erythropoietin in the treatment of the anemia due to chronic renal failure.

Administration of recombinant erythropoietin constitutes a revolution in treatment of the anemia of chronic dialysis patients. Such treatment has been anxiously awaited. Its realization has been possible thanks to the spectacular progress allowed by the newly developed techniques of recombinant genetics. Correction of this type of anemia can be obtained rapidly and permanently if treatment is continued without interruption. It is followed by a remarkable transformation of the patient's physical and psychic status. The occurrence of certain side effects (e.g., elevation of blood pressure and an increased tendency toward vascular thrombosis), however, requires increased awareness in the follow-up of patients at risk and adaptation of erythropoietin administration to individual needs.

Adolescent↗
PubMed1988

Radionuclide exploration of dialysis amyloidosis: preliminary experience.

The noninvasive diagnosis of amyloid arthropathy in dialysis patients is still uncertain. Therefore, we investigated the potential diagnostic value of the 99mTc-methylene diphosphonate scan in seven long-term hemodialysis patients suffering from chronic joint pain who had biopsy-proven osteoarticular amyloidosis of the recently discovered beta 2-microglobulin (beta 2-M) type. In six, but in none of five control patients on short-term hemodialysis, increased tracer uptake was found at the site of one or several articular and/or periarticular regions. Increased uptake at a given joint was often, but not always, associated with joint pain. It appeared to precede radiologically visible changes. In conclusion, the 99mTc-methylene diphosphonate scan may be of help in the early diagnosis of dialysis amyloidosis.

Adult↗
PubMed1988

Tissue uptake of 125I-beta 2-microglobulin (beta 2-M) in anephric animals in the presence or absence of aluminium intoxication.

In long-term haemodialysis patients a new type of amyloidosis composed of beta 2-microglobulin (beta 2-M) has recently been described. The amyloid deposition has a particular predilection for articular structures. In the pathogenesis of this complication markedly elevated plasma beta 2-M concentrations, such as those observed in anuric patients, have a role. However, other as yet ill-defined factors must also be implicated, possible candidates being aluminium intoxication and the widely used regenerated cellulose (cuprophan) membrane. In the present experimental study, we examined tissue distribution of exogenous beta 2-M after i.v. injection of 125I-beta 2-M to bilaterally nephrectomised rats. One hundred and twenty minutes after injection, most radioactivity remained in the vascular compartment. The accumulation in tissues was weak, and no predilection for a particular tissue became apparent. Interestingly, chronically aluminium-overloaded, acutely anephric rats accumulated a significantly greater amount of 125I-beta 2-M in their spleens than anephric rats without prior aluminium intoxication. We then attempted to induce beta 2-M amyloid deposition in rats and mice, some of whom had undergone chronic aluminium intoxication and subcutaneous implantation of regenerated cellulose fragments for various periods of time. They were subsequently made anephric to obtain high plasma beta 2-M concentrations. None of the animals developed beta 2-M amyloidosis in spleen, liver, skin and mechanically altered joint synovium. In conclusion, chronic aluminium intoxication enhances splenic accumulation of exogenous 125I-beta 2-M in anephric rats. The factors required to form beta 2-M-amyloidosis in vivo have still to be defined.

Aluminum↗