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Biomedical subjects

V Misefari

Publications and source records attributed to V Misefari.

6 recordsLinked to original sources

Complement activated leucopenia during hemodialysis: effect of pulse methyl-prednisolone.

We tested in vivo the effect of methyl-prednisolone (MP) on C5a release and granulocytopenia occurring early in the course of extracorporeal blood circulation through a Cuprophan dialyzer. MP boluses (30 mg/kg) were given to 10 consenting patients suffering from acute renal failure, immediately before blood started to circulate through a hollow-fiber Cuprophan dialyzer. To avoid drug loss through the dialyzer membrane, dialysate flow was withheld during the first hour of treatment and ultrafiltration was kept near zero (sham dialysis). Control procedures were carried out in a similar way, without MP. MP concentration, differential WBC count and anaphylotoxin C5a were serially measured during the procedures. MP pharmacokinetics was evaluated in six other uremic patients off dialysis. As shown by similar C5a levels in dialyzer effluent blood, complement cascade was activated by Cuprophan to a comparable degree whether or not patients received MP. Neutrophil count dropped 68% during the control procedure and 54% during sham dialysis preceded by MP (95% confidence interval of the difference, 1.97-27.2). Sham dialysis did not apparently influence serum MP levels, as shown by similar peak values in patients undergoing sham dialysis (203 micrograms/ml +/- SEM 33) and in patients off dialysis (177 micrograms/ml +/- 42). In vitro aggregometry showed that the uremic milieu does not interfere with the antiaggregating effect of MP. Our results show that MP at the dosage of 30 mg/kg does not affect complement-mediated granulocytopenia in any important way.

Acute Kidney Injury

Effect of blood cooling on cuprophan-induced anaphylatoxin generation.

We investigated whether cooling of the extracorporeal blood during hemodialysis could prevent anaphylatoxin generation and leukopenia caused by blood-cuprophan contact. After preliminary in vitro studies confirming the temperature dependence of C5a generation, we carried out hypothermic dialysis on nine patients by manipulating blood and dialysate temperature in such a way that blood temperature within the dialyzer averaged 25 degrees C. In comparison with the control procedure (blood temperature within the dialyzer 35 degrees C) hypothermic dialysis reduced peak C5a generation from 41.7 +/- 17 ng/ml to 9.7 +/- 3.4 ng/ml (P less than 0.01), and white blood cell fall from 72 +/- 15 to 25 +/- 20% (P less than 0.01). Arterial PO2 decreased less in hypothermic dialysis (-19 +/- 9% of pre-HD value) than in the control procedure (-30 +/- 11%) (P less than 0.05). We conclude that blood cooling attenuates cuprophan-induced anaphylatoxin generation and leukopenia.

Adult

Long term effects of cryoapheresis and cytostatic treatment in essential mixed cryoglobulinemia.

We studied the effects of cryoapheresis combined with different immunosuppressive treatments on the course of the glomerulonephritis of essential mixed cryoglobulinemia. The study was carried out on 11 patients. The effects of immunosuppressive treatments on cryoglobulin rebound after cryoapheresis varied widely. In those responding with sustained reduction in serum cryoglobulin levels, creatinine clearance increased, an effect that lasted several years in 4 patients. In one patient cryoglobulin disappeared, with almost fully recovery of renal function and normalization of blood pressure. One patient died of acute liver failure shortly after the first observation and another entered regular dialysis treatment. All the other patients are still alive after follow-up of 2-9 years. These results compare favourably with those reported by other investigators and suggest that cryoapheresis and cytostatic drugs are beneficial for glomerulonephritis associated with essential mixed cryoglobulinemia.

Adult

HBsAg immune complex glomerulonephritis.

Out of 97 patients with various forms of glomerulonephritis 10 were found to be HBsAg seropositive. None of these showed HBsAg immunodeposits within the kidney. Direct immunofluorescent kidney staining for HBsAg was observed in 4 out of 87 HBsAg seronegative patients. The HBsAg staining in kidneys was a false positive reaction due to binding of the Fc portion of the fluoresceinated IgG molecules to the IgM RF tissue deposits. The false positive reaction for HBsAg is not revealed by the usual specificity controls for fluorescence staining. The role of HBsAg in glomerulonephritis remains unproven.

Antigen-Antibody Complex

Selective removal of plasma cryoglobulins in cryoglobulinaemia.

Cryoglobulins were removed from the plasma of two patients with mixed cryoglobulinaemia (IgM(k)-IgG type) associated with severe membrano-proliferative glomerulonephritis and angiitis. The removal of about half the circulating cryo-Igs ('cryo-Igpheresis') was followed by a brisk rebound in cryo-Igs due to the rapid synthesis rate of monoclonal IgM(k) with anti-IgG activity. 'Cryo-Igpheresis' + cyclophosphamide treatment suppressed the rebound of cryo-IgGs, but not that of the cryo-IgMs. This differential effect was due to decrease of the antibody activity of cryo-IgMs. The clinical implications of such changes need further evaluation.

Cryoglobulins