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Biomedical subjects

R Wens

Publications and source records attributed to R Wens.

At least 19 recordsLinked to original sources

Role of complement and platelet-activating factor in the stimulation of phagocytosis and reactive oxygen species production during haemodialysis.

BACKGROUND: Neutrophil phagocytic functions have been studied extensively in haemodialysis (HD) patients; however, results are contradictory and the mechanisms that modulate phagocytosis and oxidative burst during dialysis are not completely understood. METHODS: The present study investigated neutrophil functions in a selected population of patients before and during clinical dialysis with cuprophane, and polyacrylonitrile (AN69) membranes. We measured phagocytosis of Escherichia coli and intracellular hydrogen peroxide (H2O2) production by flow cytometry in whole blood. RESULTS: Before dialysis, neutrophils from HD patients showed normal phagocytic capability and H2O2 formation. Phagocytosis of FITC-E. coli was significantly stimulated in cuprophane but not AN69-treated patients. Spontaneous and stimulated H2O2 production was enhanced with both cuprophane and AN69 membranes. We then investigated in vitro the role of complement and platelet-activating factor (PAF) in the activation of neutrophils. Incubation of whole blood with C5a increased phagocytosis but not H2O2 production. On the contrary, the addition of synthetic PAF showed a markedly stimulated H2O2 production without increase in phagocytosis. Moreover, during dialysis with formaldehyde-reused cuprophane, complement activation was abolished and phagocytosis was no longer enhanced, while the stimulation of H2O2 production persisted. In addition, we also excluded a particular role of the membrane itself in the activation of neutrophils. CONCLUSION: We demonstrated that in a selected population of HD patients, neutrophils exhibit normal phagocytic capability and normal intracellular H2O2 production. During dialysis, the stimulation of phagocytosis observed with cuprophane is complement dependent, whereas the enhanced H2O2 production observed with both cuprophane and AN69 membranes might be related to PAF production.

Complement Activation↗

[Regional anticoagulation with sodium citrate: chronic utilization in the hemodialysis patient].

We used an alternative technique for regional citrate anticoagulation (citrate 0.48 Mol; bicarbonate containing dialysate with Ca 1.75 Mmol) in three patients at chronic risk of bleeding and for a mean follow-up period of ten months. No bleeding recurrence was observed nor any complication related to citrate. Hemoglobin and hematocrit rose without transfusions. Serum bicarbonate increased during the first four months of treatment. No significant change was observed in serum calcium nor serum sodium concentration.

Aged↗

Critical role of iron overload in the increased susceptibility of haemodialysis patients to bacterial infections. Beneficial effects of desferrioxamine.

Iron overload, which is a common complication in haemodialysis patients, is known to enhance bacterial growth and virulence, and to alter phagocytosis. We reviewed the data of 61 haemodialysed patients to clarify the clinical relevance of iron status to the risk of bacterial infection. Increased concentrations of serum ferritin were associated with a greater infection rate (P less than 0.0025), which was already true for ferritin values between 500 and 1000 micrograms/l (P less than 0.025). Furthermore, in 21 iron-overloaded patients treated with an iron-chelator (desferrioxamine), the infection rate decreased from 1/19 patient-months to 1/112 (P less than 0.005), and returned to previous values when desferrioxamine was stopped. Our results demonstrate the importance of haemosiderosis in the increased susceptibility of haemodialysed patients to infections; this susceptibility is decreased by desferrioxamine therapy, which probably acts by restoring phagocytosis and reducing the bioavailability of iron for pathogens.

Aluminum↗

[Bone and joint complications in patients treated with continuous ambulatory peritoneal dialysis (CAPD) for more than 3 years].

The clinical, biochemical, radiological and scintigraphical data related to renal osteodystrophy were followed in 18 patients on CAPD for 3 to 5 years. The majority maintained normal serum calcium, bicarbonate and alkaline phosphatase concentrations; serum phosphate concentration decreased after starting CAPD but remained somewhat elevated. Only half of the patients needed phosphate binders. Serum PTH concentrations fell in those with high values at the start and remained stable in most others. Serum aluminum concentrations never exceeded 50 micrograms/l while serum 25(OH)D3 levels remained low. Bone radiology and scintigraphy were characterized by their stability over time. We think that CAPD, with the addition of calcium carbonate, phosphate binders and vitamin D analogs can achieve good control of renal osteodystrophy. In addition, joint problems are not common in CAPD patients but we present evidence that they too are at risk of dialysis amyloidosis.

Adolescent↗

Left atrial myxoma associated with systemic AA amyloidosis.

A 76-year-old woman presenting with generalized amyloidosis of the AA-type protein was found to have a left atrial myxoma. Retrospective estimation of the concentration of SAA protein, a serum precursor of AA amyloid, before and after surgical removal of the myxoma, showed that the SAA protein had disappeared after the operation. A common manifestation of myxoma is the development of a severe inflammatory syndrome that sometimes simulates rheumatic fever or bacterial endocarditis. However, to our knowledge, it has never been described in association with amyloidosis. We suggest that atrial myxoma should be added the list of neoplastic and inflammatory diseases predisposing to AA amyloidosis.

Aged↗

Continuous ambulatory peritoneal dialysis vs haemodialysis: a lesser risk of amyloidosis?

We compared plasma beta-2-microglobulin (beta 2M) at a 1-year interval in 25 CAPD patients and 25 patients haemodialysed with cuprophane membranes and matched for residual renal function and duration of renal replacement therapy. Plasma beta 2M remained lower in CAPD patients throughout the study, and increased significantly with time both in CAPD and haemodialysis patients, as renal function decreased. In both groups, plasma beta 2M was negatively correlated with residual creatinine clearance, the influence of the latter being much greater in haemodialysis, as demonstrated by comparison of the regression lines. In haemodialysis, but not in CAPD, plasma beta 2M also correlated with time on dialysis. In CAPD patients, the daily peritoneal output averaged 38 mg (range 16-59 mg), and was directly correlated with plasma beta 2M. CAPD thus allows a significant peritoneal removal of beta 2M, which progressively takes over from the declining renal function, resulting in lower plasma beta 2M than in matched haemodialysis patients. However, the peritoneal removal of beta 2M remains insufficient and values increase with time as renal function declines. Thus, if beta 2M amyloidosis is related to raised plasma levels, the risk of beta 2M amyloidosis in CAPD should simply be delayed as compared to haemodialysis.

Adult↗

Effect of aluminum on porphyrin metabolism in hemodialyzed patients.

In patients with renal failure and on chronic hemodialysis, serum aluminum, serum delta-aminolevulinic acid, serum porphobilinogen and erythrocyte zinc protoporphyrin (ZPP) are significantly elevated, whereas erythrocyte delta-aminolevulinic acid dehydratase activity (ALAD, values in percent) is significantly reduced. The last two parameters (ZPP and ALAD) are statistically related to serum aluminum concentration (Al-S), but only the correlation between Al-S and ALAD remains statistically significant after standardization for the degree of renal insufficiency (expressed in terms of urea level). This study does not support the hypothesis that the retention of aluminum is responsible for the increase of ZPP in uremic patients on dialysis. The disturbances of porphyrin metabolism found in patients with renal failure and on chronic dialysis are not similar to those observed in porphyria cutanea tarda.

Adult↗

Campylobacter fetus peritonitis followed by septicaemia in a patient on continuous ambulatory peritoneal dialysis.

A 62-year-old man being treated by continuous ambulatory peritoneal dialysis (CAPD) developed peritonitis due to Campylobacter fetus subspecies fetus (intestinalis), an organism seldom isolated in such circumstances. After appropriate and apparently effective antibiotic therapy, the patient relapsed 6 weeks later with septicaemia. Blood cultures yielded a similar organism, thereby suggesting a clinically silent metastatic infection during the episode of peritonitis, probably at an old arteriovenous fistula. Parenteral tobramycin followed by oral erythromycin achieved a complete cure of this unusual complication.

Campylobacter Infections↗

Red blood cells indices and aluminium toxicity in haemodialysis patients.

Microcytic, hypochromic anaemia is a feature of aluminium toxicity. To detect the possible influence of aluminium on erythropoiesis in a general haemodialysis population we studied the evolution of red blood cell parameters and aluminium status in 30 patients (27 without aluminium toxicity symptoms). Aluminium status was assessed by serum aluminium measurements before (BAl) and after (PAl) a desferrioxamine infusion. The evolution with time (delta) of PAl and DAl (= PAl - BAl) during the prospective study inversely correlated with delta mean corpuscular volume (2 alpha less than 0.01) and delta mean corpuscular haemoglobin (2 alpha less than 0.001). Patients with DAl greater than 180 micrograms/L had lower mean corpuscular haemoglobin values (p less than 0.05). These findings suggest that aluminium inhibits haemoglobin synthesis even in haemodialysis patients free of aluminium toxicity symptoms.

Adult↗

Bone scan in haemodialysis patients: relation to hyperparathyroidism and aluminium toxicity.

The influence of hyperparathyroidism and aluminium toxicity on bone scan scores (FS = Fogelman's score) was studied in 37 haemodialysis patients (group 1), of whom 24 had aluminium toxicity (group 2). FS, parathormone (iPTH) and aluminium status were assessed simultaneously, the latter by measuring serum aluminium before (BAl) and 48 hours after (PAl) a desferrioxamine infusion. FS correlated directly with iPTH in all groups, inversely with PAl and DAl (= PAl - BAl) in group 1; FS less than or equal to 2 was found in group 2 only (2 alpha less than 0.05). The time course of FS and aluminium concentration was also studied in 24 patients: a PAl increase was significantly associated with a FS decrease (2 alpha less than 0.001). In conclusion, hyperparathyroidism increases and aluminium toxicity decreases FS; FS less than or equal to 2 is very suggestive of aluminium toxicity.

Adult↗

Improvement of anemia with deferoxamine in hemodialysis patients with aluminum-induced bone disease.

As microcytic anemia is a feature of aluminium intoxication, we prospectively studied the hematologic effects of deferoxamine in 10 hemodialysis patients with aluminum-induced bone disease. Comparing the mean monthly results of a 4 month period before and during deferoxamine therapy, we observed an important decrease of the transfusion needs (alpha less than 0.025) and an increase of hematocrit (p less than 0.02), hemoglobin (p less than 0.02), MCV (p less than 0.02) and MCH (p less than 0.05); the number of red blood cells remained unchanged. Our results show that deferoxamine treatment of dialysis patients with aluminum bone disease can markedly improve their anemia, even in the absence of recent aggravation, microcytosis and hypochromia. They also suggest that aluminum could participate in the anemia of dialysis patients even if it is normocytic.

Adult↗