Achieving self sufficiency in blood across Europe.
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Biomedical subjects
Publications and source records attributed to J Leikola.
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Enhanced lipid peroxidation, reported to take place in rheumatoid joints and suggested to play a significant role in joint inflammation, led us to study the occurrence of antibodies against oxidised low-density lipoprotein (Ox-LDL Ab) in patients with juvenile chronic arthritis. Enzyme-linked immunosorbent assay was used to detect Ox-LDL Ab and antiphospholipid antibodies (aPL Ab) in sera from 84 patients and 91 controls. Elevated levels of Ox-LDL Ab were found in 14 patients (17%) as opposed to 4 controls (4%; p < 0.01). Similarly, 14 patients had an elevated aPL Ab level and a fairly good correlation between Ox-LDL Ab and aPL Ab (r = 0.52) existed in the patients. The increased frequency of elevated levels of Ox-LDL Ab may reflect lipid peroxidation occurring in rheumatoid joints but crossreactivity with aPL Ab for the induction of Ox-LDL Ab cannot be excluded.
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Sufficiency is the balance between supply and demand. The problems of estimating future demands and of maintaining adequate supplies of blood for the preparation of blood products, will be discussed from the viewpoint of a well-established blood transfusion service.
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Pulmonary coumarin 7-hydroxylase, testosterone hydroxylase and other P450-mediated activities were compared in the mouse and rat. Coumarin 7-hydroxylase activity was 20 pmol/mg/min. in mouse and 4 pmol/mg/min. in rat lung microsomes. Liver values were 180 (mouse) and 1 (rat) pmol/mg/min. Km values of rat and mouse lung coumarin 7-hydroxylase were about 1 microM whereas the rat liver Km value was > 100 microM. Phenobarbital and 3-methylcholanthrene did not affect rat lung (or liver) coumarin 7-hydroxylase activity. Anti-Cyp2a-5 antibody effectively inhibited mouse and rat lung coumarin 7-hydroxylase and testosterone 15 alpha-hydroxylations but failed to block these activities in the rat liver. In immunoblot analysis anti-Cyp2a-5 antibody recognized the 50-kDa Cyp2a-4/5 protein in mouse lung microsomes. A P450 protein co-migrating with Cyp2a-5 was also detected in rat lung microsomes. Cyp2a-5 cDNA probe hybridized with a 1.8-kb mRNA species in rat lung RNA fraction. The hybridization signal was not increased by 3-methylcholanthrene or phenobarbital. These data suggest that the mouse lung expresses Cyp2a-5 which differs from the liver enzyme only in its regulation and that the rat lung contains a P450 isoform(s) belonging to the 2A subfamily which may be orthologous with the mouse Cyp2a-4/5 catalyzing coumarin 7-hydroxylase and testosterone 15 alpha-hydroxylase activities. The recently reported rat lung CYP2A3 (Kimura et al.) gene product is a candidate for the observed coumarin 7-hydroxylase activity in the rat lung.
The advantages of an all-volunteer system include safety of the donor and the recipient, ethics of not selling any part of one's body, enhanced community responsibility and increased stability of the donor corps. Although recruitment of unpaid donors is more difficult and more expensive than that of paid donors, it can be carried out successfully, and reasonable needs of plasma products can be met by using voluntary donors only.
A countrywide prospective study on open-heart surgery patients was performed between 1987 and 1989 to determine the prevalence and nature of post-transfusion hepatitis in Finland. Altogether 685 coronary by-pass operation patients, who received on average 12.3 units of blood products, were postoperatively followed for 6 months. Ten blood samples were drawn from each patient. Hepatitis was diagnosed when the alanine aminotransferase values exceeded the upper normal value 2.5 times in one sample and twice in another, and non-viral causes could reasonably be excluded. Eleven hepatitis cases (1.6%) were recorded with a mean incubation period of 8.4 weeks; all represented the non-A, non-B type. The majority had mild symptoms or were asymptomatic but two became icteric. Six patients (55%) had abnormal alanine aminotransferase values for at least 6 months, which indicates possible chronicity. These 685 open-heart surgery patients received a total of 8,436 units of blood products; thus the rate of NANBH cases per 1000 units was as low as 1.3. This is less than recently reported in six other prospective studies.
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).
Prospective international studies have shown the incidence of post-transfusion hepatitis in the 1980s to vary between 2% and 31%. Rare cases of hepatitis B continue to occur despite donor screening for the hepatitis B surface antigen, but most are of the non-A, non-B type. Non-A, non-B hepatitis is typically mild and often subclinical in the acute phase but has a tendency to become chronic in about half the affected subjects. The recently characterised hepatitis C virus has been shown to cause most, if not all, transfusion associated non-A, non-B hepatitis. Hepatitis C seropositivity seems to be associated with viraemia and infectivity among blood donors, and donor screening for these antibodies has now been instituted in many countries. New assays now being developed are improving the sensitivity and specificity of this screening, which is estimated to prevent most cases perhaps 70 to 80% of post-transfusion hepatitis.
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Antibodies to hepatitis C virus, hepatitis B serology and liver enzymes were examined in 137 Finnish haemophiliac patients to detect signs of chronic viral hepatitis and its possible aetiological associations. The prevalence of raised alanine aminotransferase values was 37%. These were significantly associated with hepatitis C seropositivity but not with hepatitis B antibodies, severity of haemophilia or the type of clotting factor used in replacement therapy. The prevalence of hepatitis C seropositivity was 50%; it was significantly associated with severe haemophilia and with the use of large pool concentrates. The hepatitis C virus seems to be the major cause of chronic liver disease transmitted by clotting factors also in Finland, despite a somewhat lower seroprevalence than described elsewhere so far.
Fab fragments of a murine C3d-specific monoclonal antibody, clone 4C2, strongly inhibited the binding of H, and up to about 80% that of B, to C3b on sheep erythrocytes, as shown by using radiolabelled purified proteins. The inhibition was also detected in the fluid phase. Conversion of C3 by preformed solid phase alternative pathway C3 convertase was not affected by 4C2. Also, it did not affect the decay rate of the convertase, but reduced the decay-accelerating effect of H on it. The results suggest that the binding sites of B and H on C3b are close to each other, and their competition for binding to C3b is focused around the C3d region. In addition, 4C2 partially blocked noncovalent binding of C3b to human erythrocytes, which suggests that CR1 also binds close to the H- and B-binding region in C3b.
5,287 serum samples from 2 different sources in Finland, people possibly at risk and healthy blood donors, were tested for the presence of HTLV-I antibodies. No positive cases were found. The result suggests that this virus is not endemic in Finland. 10 cases gave repeatedly a low positive value in the enzyme immune assay (EIA) test but were confirmed negative with other tests that included western blot, passive agglutination and immunofluorescence. Four of these samples originated from healthy blood donors, 6 from other categories. Several of them showed restricted reactivity in western blots. Five HIV-positive sera, discovered during the study from people with possible risk factors, were also tested for HTLV-I but showed no reactivity.
World-wide, at least 75 million units of whole blood are collected annually. Of this amount, over 90% are collected in Europe, in the Americas and in Western Pacific. If all the blood were separated into components, there would be close to 14 million liters of plasma available for fractionation. Presently, only about 6 million liters of it are processed further. It is supplemented by 8 million liters of source plasma collected by plasmapheresis. Over 60% of source plasma comes from paid donors in U.S. Non-profit organizations fractionate 30% and commercial companies 70% of the total of 14 million liters of blood plasma. Of this, 42% are fractionated in Europe and 47% in North America.