Effects of repeated annual influenza vaccination on antibody responses against unchanged vaccine antigens in elderly frail institutionalized volunteers.

BACKGROUND: Concern about the possibility that annually repeated influenza immunizationmayinduce a lower antibody response than first vaccination. OBJECTIVE: To ascertain the cumulative effects of yearly vaccination on serological response to unaltered vaccine antigens in the elderly. METHODS: The haemagglutination-inhibiting (HI) antibody response was examined in 158 elderly institutionalized frail volunteers subdivided in 3 groups according to the sequential winters in which each subject received a trivalent inactivated influenza vaccine. The study, conducted over 5 consecutive winters (from 1998/99 to 2002/03), reports the antibody response only for sequential years (2 or 3) in which the vaccine strain examined was not altered. RESULTS: Significant increases in the values of HI antibody titres were observed after vaccination in each year examined against the different influenza vaccine strains used, except against B antigen in the second of the 3 winters studied (1999/00). The antibody responses found were not always adequate, i.e. at levels above the currently requested values for commercial vaccines (post-vaccination seroprotection rate >/=1:40, increases in geometric mean titres >/=2, positive responses >/=30% compared with pre-vaccination), probably because of old age (mean age >/=81 years) and the presence of underlying diseases in a high percentage of volunteers (>/=86%). The most frequent chronic diseases found werecardiovascular diseases (48%), endocrine disorders (19%), functional disability (10%) and pulmonary diseases (4%). The post-vaccination values observed in the sequential years were in general similar for A/H3N2 and A/H1N1 vaccine strains. A decrease, however, for some parameters at statistically significant levels, was observed against B antigen following repeated vaccine administrations. CONCLUSION: Our data seem to support the possibility of a slight impairment of HI antibody response against unaltered influenza vaccine antigens, especially for influenza strains that have circulated for prolonged periods of time. Indeed a tendency to a lower response was found only against B/Beijing antigen, introduced in the vaccine composition in the winter 1995/96, but not against the A/H3N2 and A/H1N1 vaccine strains, which weremore frequently changed.

Comparison of hemodialysis versus hemoperfusion in the clearance of high-dose methotrexate in pigs.

To evaluate the different capabilities of hemo-perfusion (HP) and hemodialysis (HD) treatment in resolving the side effects during high-dose methotrexate (MTX) therapy, an experimental comparative study was done. Under general anesthesia, 12 female Large-White pigs, 35 +/- 5 kg body weight, underwent a bilateral renal vessel ligature to create an acute renal failure and avoid the physiologic elimination of MTX. An MTX i.v. infusion was performed using a dose of 12.5 g/m2 and for a specific time according to its pharmacokinetics. The animals were divided into 2 groups of 6 animals each and connected to the extracorporeal circuit; the first group was submitted to a 1-h HP with an anion exchange resin (Dow 1X-2, Dow Chemical) and the second group to 1-h HD with capillary polysulfone fibers (F6, Fresenius). Blood samples were taken at established intervals for hematological and biochemical evaluations. The results demonstrate a higher capability of HP treatment (P < 0.001) related to HD in MTX removal.

In vitro evaluation of heparin adsorption during haemoperfusion with Dowex 1 x 2 anion exchange resin.

Haemoperfusion treatments have found clinical applications in various pathologies, even though problems due to the insufficient biocompatibility of sorbents have often limited its employment. Among these problems, there is that of heparin adsorption which can determine coagulation disorders or the necessity of a dosage correction during the extra corporeal circulation. The aim of the study was to test the influence of different methods of coating on heparin adsorption from an anion exchange resin coated with poly-hydroxyethyl-methacrylate. Eight haemoperfusion cartridges were prepared using 8 g of resin for each (4 cartridges contained resin coated by spray-coating technique and 4 coated by phase-separation one). Haemoperfusion was performed by using 600 IU of heparin (25,000 IU) corresponding to 0.12 ml in 500 ml of swine blood and a closed circuit. Blood flow rate was maintained at 15 ml/min and the circuit pressure was 70 torr during haemoperfusion. Blood samples were withdrawn at timed intervals before and after the column in order to evaluate blood heparin levels. The results demonstrated the superiority of the phase-separation technique that does not permit any interactions between adsorbent substance and drug. As a result of this, the adjustment of the dosage may not be necessary during further in vivo experiments.

Hemoperfusion--state of art.

The authors make a general review of the state of art in HP with particular reference to the history, the main field of application, and the development of specific and selective sorbents. In this text, attention is paid to the application in the immunological field comparing the therapeutical removal of toxins with different sorbents. Next, the authors describe their experimental study with hemoperfusion using coated anion exchange resins for the treatment of acute respiratory insufficiency, the correction of metabolic alkalosis in pyloric stenosis, the removal of a high dosage of antiblastic agent in conjunction with the study of heparin subtraction by coated resins and finally the development of a particular type of resin for phosphates removal in uremia. These different fields of research recognize the necessity to look for a selective exchange by hemoperfusion because the concept of the "magic filter" that removes everything is not scientifically acceptable. Some explanations are given for the behaviour of the strong anion exchange resins regarding simple or complex ions and the influence of the chemical composition of the matrix. In conclusion, the authors underline that selective removal by HP is actually underutilized considering its potency.

Hemoperfusion in chronic uremia.

Hemoperfusion is a blood purification technique involving direct contact between blood and adsorbent substances (sorbents). There are three basic kinds of sorbent: activated charcoal, immunoadsorbents, resins. Following our previous experience on charcoal hemoperfusion, a new coated anionic exchange resin for blood purification specifically designed to remove phosphates was experimentally employed in animals. 3 pigs, in which uremia had been surgically induced, underwent 6 extracorporeal hemoperfusion sessions (2 per pig) with a cartridge containing 100 gr of resin. The phosphate clearance proved satisfactory, values being 120 ml/min after 10' and around 80 ml/min after 2 hours. The biocompatibility of the resin and of the coating membrane was satisfactory. The negligible variation in pH and plasma bicarbonate during all sessions confirmed the low absorption by the tested resin of other blood anions competing with phosphate.

Chemical sorbents: official guidelines and experimental approach.

To evaluate the biocompatibility of an anionic exchange resin with active group trimethylammonium and charged with chloride ions an experimental study was performed with different tests to determine cytocompatibility, acute systemic toxicity, intracutaneous reactivity, allergic sensibilization, haemocompatibility and release of acetone, dichloromethane, quaternary amines and heavy metals (Pb, Cu, Cd) in eluate. Thus an anionic exchange resin can link all anionic substances; an ex vivo study on the participation of the dissociated sodic heparin in the anionic exchange was also conducted. In fact every time an extracorporeal circuit is made an anticoagulant must be administered to the patient and the removal of the drug could cause serious haemocoagulative problems. The results of the study showed a high biocompatibility of the resin that did not cause different significant reactions in comparison with negative control substances. The coating of the resin with poly-hydroxy-ethyl methacrilate with a separation phase technique avoided heparin removal from blood. Therefore adjustment of the dosage may not be necessary during further in vivo experiments. Future researches aiming to evaluate the the effectiveness and the biocompatibility of the sorbent in a living being will be performed in the next steps of the study.

In vivo experimental models on the evaluation of haemoperfusion.

We described some experimental models that were performed in rabbits and in swine in order to evaluate the efficacy of haemoperfusion treatment in hypochloremic alkalosis, uraemia and cytotoxic drug poisoning. In all the models, an extracorporeal circuit was used constituted mainly by a hematic sampling line and a cartridge, containing an anion exchange resin. Access to the blood stream was achieved by isolation and catheterization of the vessels either of the neck or of the leg, or both. The experimental model for the evaluation of haemoperfusion in hypochloremic alkalosis was carried out in rabbits by a pyloric stenosis because its size and weight are similar to new-born humans and its stomach is a simple monogastric one. The hypochloremia and alkalosis were achieved in only 4 hours. The other two experimental models were carried out in pigs because, in these cases, it was better to choose a large size animal with a nutritional similarity to humans, and with the capability to produce a stable chronic renal failure. The pigs were submitted to a bilateral ureter ligature to create a chronic renal failure or to a bilateral renal vessel ligature to avoid the physiologic precipitation of some drugs in renal tubules.

In vitro and ex vivo evaluation of methotrexate removal by different sorbents haemoperfusion.

The administration of high doses of Methotrexate (HDMTX) seems to be very effective in neoplastic treatment. Furthermore high doses of the drug could overcome the Methotrexate (MTX) resistance that it is possible to observe in some kind of cancers. To avoid several serious problems in the therapeutical application of HDMTX such as nephrotoxicity, hepatotoxicity and the difficulty to assess the right therapeutic range of the specific antagonist Leucovorin, a Haemoperfusion (HP) treatment could be very usefulL. In this study 3 anion exchange resins with different active group (trimethylammonium, dimethylethanolammonium and dimethylammina) and a spherical petroleum based charcoal were tested both in vitro and ex vivo to evaluate their capability to remove MTX. These results show a good strength and biocompatibility of the 4 sorbents and demonstrate the active group trimethylammonium resin as the most effective one.

Hemoperfusion with a new anion exchange resin corrects the metabolic alkalosis in pyloric stenosis: an experimental demonstration.

An experimental model of hypertrophic pyloric stenosis was made by suture of the pyloric wall and gastrostomy in 10 rabbits under general anesthesia. Blood sampling indicated severe alkalosis and hypochloremia 3h 30 min after surgery. To correct the derangement, we tested an ion exchange resin (Dowex SAR), coated with a methacrylic hydrogel. A cartridge containing 18 g of this resin was inserted in an extracorporeal circuit. This chloride charged resin achieved uptake of HCO3- ions, and elution of Cl- ions. The electrolytic balance was fully restored after 10 min of treatment.

Phosphate removal by resin hemoperfusion efficacy and biocompatibility of a new exchange resin.

A new coated anionic exchange resin for blood purification specifically designed to remove phosphates was experimentally employed in animals. 3 pigs, in which uremia had been surgically induced, underwent 6 extracorporeal hemoperfusion sessions (2 per pig) with a cartridge containing 100 gr of resin. The phosphate clearance proved satisfactory, values being 120 ml/min after 10' and around 80 ml/min after 2 hours. The biocompatibility of the resin and of the coating membrane was satisfactory. The negligible variation in pH and plasma bicarbonate during all sessions confirmed the low absorption by the tested resin of other blood anions competing with phosphate.

Study of the hemocoagulative parameters in hemoperfusion on polymer coated resins.

A hemoperfusion column containing anionic exchange resin coated with a new polymer has been tested in vivo for blood compatibility. The hemocoagulative parameters, evaluated before and after the cartridge during hemoperfusion, did not show any significant alteration even as regards the number and the functionality of the platelets nor as regards a possible activation of the fibrinolysis process. On the basis of these results, the hemoperfusion system examined can be regarded as hemocompatible from the hemocoagulative standpoint.