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The aim of the present study was to evaluate the lipid profiles (total cholesterol, triglycerides, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and the electrophoretic low-density lipoproteins and high-density lipoproteins) in patients with subclinical (n = 52) and overt hypothyroidism (n = 18) in comparison to normal controls (28 and 18, respectively), matched for age, sex and body mass index. Subclinical hypothyroidism was defined as a syndrome with normal free thyroxine and total thyroxine but elevated basal thyrotrophin levels and/or an exaggerated TSH response to oral thyrotrophin releasing hormone. In subclinical hypothyroidism there was an elevated LDL concentration (P less than 0.01), a diminished HDL fraction (P less than 0.05) and a borderline elevated LDL-C (not reaching the limit of significance, P = 0.07). Total cholesterol and triglyceride concentrations remained unaltered. For the whole group of patients and controls significant negative correlations were found between LDL-C and T4 (P less than 0.04), total cholesterol and free thyroxine-index (P less than 0.01); positive correlations could be demonstrated between LDL-C and basal TSH (P less than 0.03), the ratio total cholesterol/HDL-C and basal TSH (P less than 0.03), and triglycerides and basal TSH (P less than 0.01). Our data provide a possible explanation for the higher prevalence of coronary heart disease reported in subclinical hypothyroidism. There may well be a case for the detection and early treatment of such individuals.

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Hepatitis A virus (HAV) was purified from MRC-5 human diploid cell cultures, inactivated with formalin, and evaluated for safety and immunogenicity in humans. Three vaccine formulations were produced: (a) a fluid preparation containing inactivated HAV, (b) inactivated HAV adsorbed to Al(OH)3, and (c) inactivated HAV coupled to novel immunopotentiating reconstituted influenza virosomes (IRIV). IRIV were prepared by combining phosphatidylcholine, phosphatidylethanolamine, phospholipids originating from the influenza virus envelope, influenza virus hemagglutinin, and neuraminidase. The HAV-IRIV appeared as unilamellar vesicles with a diameter of -150 nm when viewed by transmission electron microscopy. Upon intramuscular injection, the alum-adsorbed vaccine was associated with significantly (P < 0.01) more local adverse reactions than either the fluid or IRIV formulations. 14 d after a single dose of vaccine, all the recipients of the IRIV formulation seroconverted (2 20 mIU/ml) versus 30 and 44% for those who received the fluid and alum-adsorbed vaccines, respectively (P < 0.001). The geometric mean anti-HAV antibody titer achieved after immunization with the IRIV-HAV vaccine was also significantly higher (P < 0.005) compared with the other two vaccines. (J. Clin. Invest. 1992. 90:2491-2495

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Immunopotentiating reconstituted influenza virosomes (IRIV) are efficient carrier systems for small virion particles such as hepatitis A virus (HAV). We evaluated immunogenicity and tolerability of an IRIV-HAV vaccine and the effectiveness of a booster by immunising 104 healthy HAV seronegative volunteers. A single dose was highly immunogenic, since 98% of volunteers had seroconverted after 2 weeks. Anti-HAV titres remained high, with 100% seroconversion rate 1 year later, when the booster was given. The vaccine was effective, with a 22-fold increase in geometric mean titres 1 month later. No serious adverse reactions were observed.