Search

Background: Clinical and pharmacokinetic data suggest that very low doses of subcutaneous recombinant human erythropoietin (rHuEPO) may be effective in a preoperative autologous blood deposit program. Study Design and Methods: Fifty-two patients, scheduled for orthopedic surgery, were enrolled in a double-blind and placebo-controlled study. Patients were randomly assigned to the placebo group or to receive 30, 60, or 100 IU per kg of rHuEPO subcutaneously twice a week for 2 weeks before surgery. The dose of rHuEPO that was effective in facilitating the collection of 4 units of blood in the 2 weeks before surgery and that prevented a sharp decrease in hematocrit was determined. Results: Only in patients receiving 100 IU per kg of rHuEPO did the outcome measurements differ significantly from those in the placebo group. With a higher (p < 0.01) cumulative increase in red cell volume during the study period (297 ± 127 vs. 121 ± 44 mL), 64 percent of those receiving 100 IU per kg of rHuEPO were able to donate 4 units of blood for autologous use, as compared with 23 percent of the placebo group (p < 0.05). Allogeneic transfusion was avoided, and the preoperative hematocrit and reticulocyte count were significantly higher in the patients receiving 100 IU per kg of rHuEPO (p < 0.05 and p < 0.01, respectively). Conclusion: Subcutaneously administered rHuEPO at a dose of 100 IU per kg twice a week for 2 weeks is effective in facilitating the collection of blood for autologous use and may improve the cost-benefit ratio of blood conservation interventions. Doses ≤ 60 IU per kg are ineffective in facilitating such collections in this surgical setting.

Although lipoprotein abnormalities of the nephrotic syndrome are assumed to be related to the presence of proteinuria, this topic has not been investigated extensively. We measured lipoproteins from 19 nonuremic patients during and after remission of the nephrotic syndrome in an effort to determine the extent of their putative atherogenicity. As expected, disturbances involved primarily the apoprotein B-containing lipoproteins. No patient showed serum lipoprotein(a) [Lp(a)] < 300 mg/L during the acute phase. Lp(a) concentrations correlated significantly with those of apoprotein B, and both values decreased dramatically with the remission of the nephrotic syndrome. Surprisingly, despite the resolution of proteinuria, concentrations of intermediate-density lipoproteins and Lp(a) remained above normal in hypertriglyceridemic patients, suggesting a residual effect of nephrosis in the overall lipoprotein transport. Accumulation of atherogenic remnants should be considered a characteristic of the hyperlipidemia of the nephrotic syndrome, and aggressive treatment to reduce proteinuria is mandatory.

A considerable demand for convenient, rapid, inexpensive assays of ferritin in serum has been generated in recent years in hospital laboratories and blood banks. We describe a simple and rapid particle-enhanced turbidimetric immunoassay suitable for routine application in a Monarch 2000 centrifugal analyzer with commercially available reagents. This fully automated assay (y) requires no pretreatment of sample, and correlation with a two-step sandwich ELISA (x) is excellent (y = 1.018x + 0.397, Sy/x = 0.027). The analytical range extends from 5 to 900 micrograms/L. Intraassay imprecision (CV) ranged from 1.1% to 5% for various specimen concentrations. Interassay imprecision ranged from 2.2% for above-normal concentrations (755 micrograms/L) to 9.5% for low concentrations (39 micrograms/L). No specimen-related carryover was detected. The method has been useful in our predeposit autologous blood transfusion program for rapid assessment of iron status in patients undergoing repeated phlebotomies.

We have investigated the influence of variation of the concentrations of serum albumin and immunoglobulins on serum fructosamine concentration in 33 patients with nephrotic syndrome, and 18 patients with cirrhosis of the liver. Protein alterations were evident in these patients and they were compared with 109 normal subjects, 43 patients with type II diabetes mellitus and nine diabetic patients with nephrotic syndrome. The mean serum fructosamine concentration in diabetic patients (2·76±0·53 mmol/L) was significantly increased ( P < 0·001) by comparison with normal subjects (1·93 ±0·20 mmol/L) and the other patients studied. Patients with diabetic nephropathy had higher ( P < 0·01) serum fructosamine concentrations (2·23± 0·54 mmol/L) than non-diabetic patients with the nephrotic syndrome (1·57 ± 0·37 mmol/L) but remained with the normal range. Positive correlations were observed between fructosamine and immunoglobulins G and M in nephrotic and cirrhotic patients. Serum immunoglobulin A was also directly correlated with serum fructosamine in patients with cirrhosis of the liver. An inverse correlation between albumin and fructosamine in serum of patients with cirrhosis of the liver was also noted. We conclude that the fructosamine assay is not useful in the assessment of glycemic control in patients with cirrhosis of the liver, nephrotic syndrome or in any other clinical situation in which protein metabolism is altered.

There is considerable evidence to suggest that plasma lipoprotein(a) [Lp(a)] concentration is a cardiovascular risk factor. Confusing results in epidemiologic studies, however, suggest that the effects of storage should be further investigated. The influence of the assay method, the initial plasma Lp(a) concentration, and the apolipoprotein(a) [apo(a)] genotype are all factors that should be considered.Blood was obtained from 65 survivors of premature myocardial infarction and 95 age-matched controls. The plasma samples were stored in sterile conditions at -70 degrees C for 5 years in the presence of antioxidant and antiproteolytic substances. Plasma Lp(a) was measured by immunoturbidimetry, and apo(a) alleles were determined by pulsed-field gel electrophoresis and Southern blotting.Plasma Lp(a) was significantly higher in patients. The mean kringle number for the smallest isoform was also lower in patients than in controls, but no differences were found in the distribution of the largest isoform. All patients and controls were heterozygotes. During storage, mean Lp(a) decreased significantly in samples from patients (-23%; P0.001) but not in samples from controls (-9%; P, not significant). This was not related to the kringle number and was limited to samples with initial plasma Lp(a) concentrations between 41 and 345 mg/L.Plasma Lp(a) from patients is less stable than Lp(a) from controls, and the difference is not related to distribution of apo(a) genotypes but may be concentration-dependent. Differential sample stability may complicate the interpretation of several studies.

Platelet glycoprotein IIb/IIIa may be involved in the pathogenesis of myocardial infarction as the key element in platelet aggregation and as the binding site of lipoprotein(a) to platelets, inhibiting plasminogen binding and activation. Recently, a strong association between the P1A2 polymorphism of the glycoprotein IIIa gene and acute coronary thrombosis has been reported. although this has not been confirmed. In an associated study, we determined plasma lipoprotein levels, the apo E genotype and the P1A genotype in 250 males under 55 years with myocardial infarction and they were compared with 250 age- and sex-matched controls. Patients showed an over-representation of the epsilon3/4 genotype with respect to the control group. We found that there were no differences in the allelic frequency of P1A2 between case patients and age-matched controls (chi2 = 0.05, P = 0.92) and that subjects bearing the P1A2 allele showed higher plasma lipoprotein(a) concentration than p1A1/P1A1 individuals. Therefore, in this population there is no association between carriage of p1A2 allele and increased risk of myocardial infarction but the carriage of P1A2 is associated with higher plasma Lp(a) concentration.

The concentrations of 25 plasma proteins were measured in 22 patients with membranous nephropathy. For some large proteins, the plasma concentrations were increased; there were also large proteins with low plasma concentrations, but small or medium-sized proteins showed uniformly lower plasma concentration than the controls. Plasma colloid osmotic pressure (π) and viscosity (η) were not interrelated but showed positive and significant correlations with plasma concentrations of small and medium-sized proteins (π) and plasma concentrations of large proteins (η), respectively. Nephrotic plasma is not efficient in maintaining plasma π but highly efficient in maintaining plasma η. High plasma fibrinogen concentrations and low antithrombin III concentrations may predispose to thrombosis, and low IgG concentrations may account for the higher predisposition to bacterial infection. The relative composition of nephrotic plasma is heavily dependent on the size of the different proteins. Plasma π and η are also maintained by the relative preponderance of different plasma proteins.

Lipoprotein measurements in a group of 29 patients with massive proteinuria and without hypoalbuminemia, were compared with those observed in matched controls and patients with overt nephrotic syndrome to assess the influence of plasma albumin concentration and proteinuria in modulating blood lipid levels. Plasma apoprotein B and apo B containing lipoproteins were not increased in proteinuric normoalbuminemic patients. There was a good correlation between plasma albumin and oncotic pressure (r = 0.937; P < 0.001). Plasma oncotic pressure was inversely correlated with plasma apoprotein B in nephrotic patients (r = -0.44, P = 0.017) but not in normoalbuminemics (r = 0.17, P = 0.369), suggesting that plasma albumin affects apoprotein B secretion. Other findings, however, indicate that multiple processes are ocurring simultaneously in these patients. There was an accumulation of very low- and intermediate density lipoproteins in normoalbuminemics, suggesting a residual defect in the lipoprotein removal. Also, raised (P < 0.05) lipoprotein(a) levels respect to controls (median, 0.15 g/l) were noted in both, normoalbuminemics (median, 0.72 g/l) and hypoalbuminemics (median, 0.84 g/l) with similar degree of proteinuria (6.4 vs. 6.6 g/24 h), suggesting that other mechanisms may be operative in lipoprotein(a) derangements. Our findings suggest that there is no unique mechanism in the pathogenesis of nephrotic hyperlipidemia but that both hypoalbuminemia and proteinuria can have a distinct contribution, individually or in combination.

The effect of lovastatin on the hyperlipidemia induced in rats with experimental nephrotic syndrome was investigated; toxicity and the effects on common blood chemistry parameters were also assessed. Hyperlipoproteinemia in this particular model is associated with an increase in hepatic synthesis of lipoproteins, and treatment with lovastatin could be the most suitable, since the drug inhibits cellular cholesterol synthesis. Lovastatin treatment resulted in a considerable reduction in plasma cholesterol and triglyceride levels. The decrease in cholesterol levels with treatment was mainly confined to the low-density lipoproteins (LDL) although there was a reduction in the nephrotic-syndrome-induced incremental level of high-density lipoprotein cholesterol. Other lipoprotein fractions were unaffected by lovastatin. LDL apoprotein B was increased in both groups of rats, but to a lesser degree in the lovastatin-treated group, suggesting a double effect, inhibition of both, cholesterol and apoprotein synthesis. Both groups of rats showed a certain degree of renal impairment as shown by significant elevations in plasma urea and creatinine levels. Hepatic damage was also observed, chemically and microscopically, in both groups of rats, being more pronounced in those rats treated with lovastatin in which a 50% mortality ensued after 2 weeks of treatment. At the dosage used this may have some implications in its therapeutic use in certain conditions.