Clinical experience with inactivated, virosomal influenza vaccine.

Current available influenza vaccines are safe and effective in preventing influenza. Nevertheless, there is a need for influenza vaccines with improved efficacy in the elderly. This need is underscored by both the observation that influenza has a major clinical and economic impact in the elderly and the fact that currently available vaccines are generally less effective in elderly than in younger subjects. Several approaches are currently being pursued in order to improve the efficacy of influenza vaccines in elderly individuals and others who have impaired immune responses to conventional influenza vaccines. A novel antigen-presenting strategy to overcome impaired immune responses is the use of virosomes. Previously, data on safety and reactogenicity have been published regarding the use of virosomal influenza vaccines. Data from three recent clinical trials are presented here. The first of these was a comparative study of a virosomal vaccine and a conventional subunit vaccine in "at-risk" adults with underlying chronic illness. The virosomal vaccine demonstrated comparable tolerability to the subunit vaccine, with about 98% of patients reporting tolerability to be good or very good. The vast majority of adverse events reported were mild to moderate in severity. With both vaccine types, mean HI titres decreased with age for both the A-H1N1 and B influenza virus strains, but for the A-H3N2 strain (the most virulent of the three strains), mean HI titres did not decrease with age, suggesting a better response with the virosomal vaccine when compared to the subunit vaccine. All three studies explored the long-term persistence of antibodies after vaccination with virosomal influenza vaccines. Immunogenicity declined over time but remained high at 4, 6 and 12 months post-vaccination compared to baseline, indicating that adequate seroprotection is achievable for the duration of the influenza season. Virosomal vaccines may induce better immunity in elderly subjects and may be more effective in reducing morbidity and mortality in this age group.

Focal cerebral ischemia in the mouse: hypothermia and rapid screening of drugs.

1. We have investigated the ability of several compounds to diminish both infarct area and volume induced by middle cerebral artery occlusion in the mouse. 2. Lifarizine, ipsapirone and N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine HCl (DPPE) all reduced both infarct area and volume. Ifenprodil diminished the infarct area, but the effect on total infarct volume was much less pronounced. 3. In addition, we tested the protective effects of some other drugs on infarct area only. Nimodipine, verapamil, diltiazem, N-[1-[4-(4-fluorophenoxy)butyl]-4-piperidinyl]-N-methyl-2-benzothiazo lamine (R56865) and sabeluzole had no effect on infarct area. (S)-Emopamil significantly diminished infarct area. 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) also diminished infarct area significantly. 4. In some brain ischemia models hypothermia protects against ischemic damage. Mild hypothermia had no effect on infarct area in the present mouse model of focal ischemia.

The effect of dopamine on the occurrence of kidney lesions caused by hypotension in rats.

Dopamine at dose rates varying from 80 micrograms/kg/min to 0.3 micrograms/kg/min was infused i.v. in rats anesthetized with ketamine, during a period of 60 min while the rats were bled into a reservoir against a pressure of 50 mm Hg. The bleeding was followed by reinfusion of the blood remaining in the reservoir at 60 min. At a dose rate of 80 micrograms/kg/min 5/9 animals died during the bleeding and the remaining 4 died within 24 hr. In all 9 animals the time at which the bleeding volume reached its maximum (tMBV in.) was shortened considerably and spontaneous uptake of shed blood started earlier than in the controls. At 20 micrograms/kg/min 24 hr mortality was 63% and tMBV in. was shortened. At 5 micrograms/kg/min and lower 24 hr mortality was negligible, but at 5 micrograms/kg/min tMBV in. was still shortened. At all doses used the maximum bleeding volume was essentially the same. At 20 micrograms/kg/min and lower no significant effect on the severity of kidney lesions was observed. The absence of a favourable effect of dopamine may largely be explained by the high sympathetic tone present during the period of hypotension.

The possible role of catecholamines in the protective effect of general anesthetics against kidney lesions in rats subjected to hemorrhagic hypotension.

Dibenamine, 15 mg/kg, injected i.p. in rats anesthetized with ketamine, 60 min before bleeding for 60 min against 40 mm Hg, significantly reduced the severity of kidney lesions. The maximum bleeding volume was reduced by 14%. Adrenalectomy also reduced the bleeding volume but all animals died within 24 hr. In unanesthetized rats bled against 40 mm Hg, plasma adrenaline and nor-adrenaline rose approximately tenfold as compared with unbled animals. Comparable marked increases in plasma adrenaline and somewhat smaller increases in plasma nor-adrenaline were observed after bleeding rats anesthetized with ketamine and ethylurethane, anesthetics which protect only slightly against the occurrence of kidney lesions. The rise in plasma adrenaline and nor-adrenaline was significantly lower after bleeding rats anesthetized with the highly protective anesthetics Na-pentobarbital, halothane and methoxyflurane. If, however, rats anesthetized with Na-pentobartical were bled for 40 min against 25 mm Hg, a situation in which the occurrence of kidney lesions is not prevented, the plasma concentration of both catecholamines was as high as in unanesthetized rats bled against 40 mm Hg. It is concluded that vasoconstriction due to the release of catecholamines is an important factor in the generation of kidney lesions during hypotension in rats and that the protective effect of a number of general anesthetics largely depends on their ability to suppress the release of catecholamines.