Freja Ebeling

Apolipoprotein E polymorphism, serum lipids, myocardial infarction and severity of angiographically verified coronary artery disease in men and women.

In several populations, the apolipoprotein E (apo E) allele epsilon 4 is associated with high concentration of plasma total and low density lipoprotein (LDL)-cholesterol and coronary artery disease (CAD). We determined the apo E phenotypes of 309 patients with angiographically verified CAD and 38 patients without CAD by isoelectric focusing and Western blotting. In men with CAD, the plasma total and LDL-cholesterol increased according to apo E phenotype in the following order: E3/2 < E3/3 < E4/3 < E4/4 (P = 0.03 for total cholesterol, P = 0.007 for LDL-cholesterol). In women, there was a similar trend (P = 0.22 for total cholesterol, P = 0.15 for LDL-cholesterol). The relative frequency of men with three vessel CAD increased (P = 0.43) together with LDL-cholesterol levels (P = 0.05) according to apo E phenotype E3/2, E3/3, E4/3, E4/4. Total and LDL-cholesterol levels were higher in patients with three vessel CAD than in patients with less serious types of CAD (P = 0.02 for total cholesterol, P = 0.007 for LDL-cholesterol). The relative frequency of patients with myocardial infarction increased according to apo E phenotype (P = 0.51). Both in men and women, there were no differences between apo E phenotypes in age at occurrence of the first myocardial infarction. The apo E allele frequencies of patients with CAD vs. without CAD were 2.3% vs. 1.3% for epsilon 2, 79.0% vs. 76.3% for epsilon 3 and 18.7% vs. 22.4% for epsilon 4. There were no statistically significant differences in apo E allele or phenotype frequencies between patients with CAD and without CAD or between patients with CAD and the general Finnish population. Our results support previous studies in suggesting that the apo E allele epsilon 4 is a risk factor for atherosclerosis, which affects plasma total and LDL-cholesterol. In addition, our results suggest that the apo E allele determines the severity of CAD.

Non-transferrin-bound iron during allogeneic stem cell transplantation.

Hydroxyl radical formation catalysed by non‐transferrin‐bound iron (NTBI) might contribute to transplantation‐related complications. The occurrence of NTBI in 10 adult allogeneic stem cell transplantation (SCT) patients was followed for 20 d. The transferrin saturation reached 99% on d −4 and remained > 80% thereafter. NTBI, measured as bleomycin‐detectable iron, was detected for 6–18 d in all patients with a peak on d −4. High transferrin saturation levels were associated with the appearance of NTBI with a threshold at 80% saturation. Prevention of the potential deleterious effects of NTBI might reduce transplantation‐related morbidity.

Apotransferrin administration prevents growth of Staphylococcus epidermidis in serum of stem cell transplant patients by binding of free iron

We investigated the effect of free, non-transferrin-bound iron occurring in haematological stem cell transplant patients on growth of Staphylococcus epidermidis in serum in vitro, and prevention of bacterial growth by exogenous apotransferrin. S. epidermidis did not grow in normal serum at inoculated bacterial densities up to 10(3) cfu ml(-1) but slow growth could be detected at higher initial inocula. Addition of free iron abolished the growth-inhibitory effect of serum, whereas addition of apotransferrin again restored it. Appearance of free iron and loss of growth inhibition coincided in patient serum samples taken daily during myeloablative therapy. Intravenously administered apotransferrin effectively bound free iron and restored the growth inhibition in patient sera. The results suggest that exogenous apotransferrin might protect stem cell transplant patients against infections by S. epidermidis and possibly other opportunistic pathogens.

Epidemiology of the Hepatitis C Virus

According to WHO estimations, about 3 % of the world population may be infected with the hepatitis C virus. The relative prevalences of subtypes of this virus vary in different geographic areas. The main known routes of transmission are parenteral; intravenous drug abuse, contaminated injection devices and receipt of unscreened blood. Sexual, vertical, household and nosocomial transmissions may occur, but seem to be rare. The risk of screened blood or blood products is now almost eliminated, but unscreened blood is a considerable risk in areas where screening is economically not possible. The future impact of this virus is greatly dependent on the trends in intravenous drug use as well as the possible emergence of increased late morbidity among present asymptomatic carriers during the next decades.

Effective binding of free iron by a single intravenous dose of human apotransferrin in haematological stem cell transplant patients

Summary. Myeloablative treatment results in iron accumulation and the appearance of non‐transferrin‐bound iron (NTBI) in the circulation, which may contribute to treatment‐related organ damage and susceptibility to infections. The aim of this study was to investigate the efficacy of human apotransferrin in the binding of NTBI in patients receiving an allogeneic stem cell transplant after myeloablative conditioning. A single intravenous 100 mg/kg dose of apotransferrin was given to six adult patients on d 3 after the transplantation. Initially, all patients had serum transferrin saturation above 80% and NTBI in their serum. After the apotransferrin injection, serum NTBI became undetectable in all patients and transferrin saturation decreased to 30–50%. Serum transferrin increased by an average of 1·95 g/l. The administered apotransferrin was subsequently converted into monoferric and diferric transferrin forms. NTBI reappeared and transferrin saturation again exceeded 80% 12–48 h after the injection in four patients and after 6 d in one patient. NTBI remained non‐detectable for the whole 12 d follow‐up period in one patient. The apotransferrin injection was well tolerated and no adverse events with probable association with the apotransferrin were observed. Repeated apotransferrin infusions might completely eliminate NTBI and iron‐induced toxicity during myeloablative therapy.

Factors predicting interferon treatment response in patients with chronic hepatitis C: late viral clearance does not preclude a sustained response

OBJECTIVES: Because of the suboptimal efficacy, cost, and adverse effects of interferon in chronic hepatitis C (HCV), predictors have been sought to detect patients with a good treatment response. Also, markers for determining a poor response early in the course of therapy, such as the lack of early viral clearance, have been proposed. METHODS: Ninety-seven patients with chronic hepatitis C were enrolled to receive leukocyte α-interferon according to a stepped-care management protocol. The final virological treatment response was evaluated in 74 patients after a 6-month post-treatment follow-up. The relationship between pretreatment and during-treatment variables and the long-term response was assessed. RESULTS: Non-1 viral genotype, higher pretreatment ALT levels, and lower γ-glutamyl transferase (GGT)/ALT ratios and GGT as well as younger age were significantly associated with a sustained response; a trend was also detected for lower serum ferritin levels. Normalization of ALT by 3 months was also a significant predictor of a long-term response. Of the 27 patients carrying the HCV genotype 3a, seven (26%) were still HCV RNA positive at 6 months. Of these patients, however, five (19%) still achieved a sustained virological response after treatment for up to 12 months. CONCLUSIONS: In contrast to some previous reports, our results suggest that a late viral clearance after 6 months of interferon monotherapy may not preclude a favorable long-term response after a 12-month treatment, especially in patients carrying a non-1 HCV genotype. A low pretreatment GGT/ALT ratio is a predictor of a good treatment response.

Beta-2-glycoprotein I antibodies in patients with thrombosis.

The laboratory diagnosis of antiphospholipid antibody syndrome currently requires two consecutive positive results in either lupus anticoagulant or anticardiolipin antibody assays. Antibodies against beta‐2‐glycoprotein I (aβ2‐GPI) are suggested as a new marker for the syndrome. The inclusion of aβ2‐GPI in the official diagnostic criteria has so far been precluded owing to lack of an international standard and also technical difficulties. Samples from 5367 consecutive patients sent to a national reference laboratory mainly because of various thrombotic events were studied. An IgG aβ2‐GPI ELISA assay was performed in addition to lupus anticoagulant (dRVVT and PTT‐LA) and IgG anticardiolipin antibody determinations to evaluate patient groups in which the new assay might be of value. From a total of 90 patients, 2.2% of the samples were aβ2‐GPI positive; 51 patients had aβ2‐GPI as the only positive antiphospholipid antibody marker; 20 patients had had a venous thrombosis and 14 an arterial thrombosis, 4 had pregnancy complications and 2 had thrombocytopenia. Relatively young patients with cerebrovascular ischaemic events seemed especially to present sole aβ2‐GPI positivity. The aβ2‐GPI positivity remained fairly constant in the 23 patients from whom follow‐up samples were taken. It is concluded that the IgG aβ2‐GPI assay seems to be a potentially important additional diagnostic tool for the antiphospholipid antibody syndrome.

Transmission of Hepatitis C Virus to Sexual Partners of Seropositive Patients with Bleeding Disorders: A Rare Event

Sexual transmission of hepatitis C virus (HCV) was studied in 30 partners to anti-HCV positive multitransfused patients with a bleeding disorder. Anti-HCV ELISA C-100 was used as a screening test. Positive results were confirmed with the first generation RIBA test. Indeterminate samples were tested also with the second generation RIBA to verify the positivity. The time of sexual exposure added up was at least 95 years. 29 partners were anti-HCV seronegative. Only 1 partner was anti-HCV indeterminate. Thus sexual transmission of HCV was a rare event.

Tolerability and kinetics of a solvent-detergent-treated intravenous immunoglobulin preparation in hypogammaglobulinaemia patients.

The tolerability and kinetics of a solvent‐detergent‐treated 6% intravenous immunoglobulin (IVIG) preparation were studied in 15 hypogammaglobulinaemia patients during 3–4 regular substitution infusions of 9–18 g, the mean dose being 359 mg/kg. The infusions were well tolerated, and the trough serum IgG levels achieved were comparable to two commercial IVIG preparations. The stepwise increase of the infusion rate up to 5 mg/kg/min and the use of this IVIG as a 12% solution were possible without serious adverse events in all the 6 studied hypogammaglobulinaemia patients. This greatly reduced the time needed for the infusions.

Post-transfusion hepatitis C in Finland

Summary. Six of 11 (55%) non‐A, non‐B hepatitis (NANBH) patients seroconverted to hepatitis C virus antibody (anti‐HCV) positivity 8–16 weeks after transfusions in a prospective post‐transfusion hepatitis study on 685 open‐heart surgery patients in Finland. Five of them had a seropositive donor, and two of the five non‐converted NANBH patients had received an anti‐HCV positive unit. Among 36 studied donors who were positive in the anti‐HCV ELISA, reactivity of both the antigen bands in a recombinant immunoblot assay (RIBA) for anti‐HCV was significantly associated with NANBH (P < 0·00005) in the recipient. In addition, infective anti‐HCV positive donors had raised ALT values more often than seropositive donors which caused no seroconversion or infection in the recipients (P= 0·0001).