Equine autologous platelet concentrates: A comparative study between different available systems.

REASONS FOR PERFORMING STUDY: Autologous platelet concentrates (APCs) are being used increasingly in horses to enhance regeneration in tissues that have poor natural healing capabilities. Numerous APC systems, which are based on different preparation techniques and were originally developed for human patients, are now routinely used in equine cases. However, preliminary process validation and adequate in vitro biochemical characterisation of most of these systems do not exist for horses. OBJECTIVES: To compare haematological findings and growth factor concentrations of equine APCs obtained with 4 commercially available systems and a noncommercial double-centrifugation technique. STUDY DESIGN: Nonrandomised in vitro experiment. METHODS: Blood samples from 6 horses were processed to produce APCs using one equine-specific filtration-based and 4 different centrifugation-based techniques. Platelet, leucocyte, platelet-derived growth factor-BB and transforming growth factor-ß1 concentrations were measured in all APCs, and their respective enrichment factors were compared. RESULTS: Mean platelet concentration increased in all systems in comparison to baseline; however, the mean enrichment factor, which ranged from 130% to 527% depending on the APC, was statistically significant in only 2 products. One method reduced total leucocyte counts to 9% of the baseline value, while the others had a mean fold increase varying from 116 to 663% of the baseline. Differential leucocyte count also differed between the products. Moreover, the various systems had significantly different mean growth factor enrichments (184-1255% for platelet-derived growth factor-BB and 93-560% for transforming growth factor-ß1 ). CONCLUSIONS: Haematological and biochemical characteristics varied markedly among 5 techniques used in the field to produce APCs in horses. These discrepancies could have an impact on clinical outcomes, and further studies are needed to determine their influence on the quality of tissue regeneration. Clinicians should not rely on the manufacturers' data relating to human patients to select the most appropriate method for horses.

Evolution of microstructure in mixed niobia-hybrid silica thin films from sol-gel precursors.

The evolution of structure in sol-gel derived mixed bridged silsesquioxane-niobium alkoxide sols and drying thin films was monitored in situ by small-angle X-ray scattering. Since sol-gel condensation of metal alkoxides proceeds much faster than that of silicon alkoxides, the incorporation of d-block metal dopants into silica typically leads to formation of densely packed nano-sized metal oxide clusters that we refer as metal oxide building blocks in a silica-based matrix. SAXS was used to study the process of niobia building block formation while drying the sol as a thin film at 40-80°C. The SAXS curves of mixed niobia-hybrid silica sols were dominated by the electron density contrast between sol particles and surrounding solvent. As the solvent evaporated and the sol particles approached each other, a correlation peak emerged. Since TEM microscopy revealed the absence of mesopores, the correlation peak was caused by a heterogeneous system of electron-rich regions and electron poor regions. The regions were assigned to small clusters that are rich in niobium and which are dispersed in a matrix that mainly consisted of hybrid silica. The correlation peak was associated with the typical distances between the electron dense clusters and corresponded with distances in real space of 1-3 nm. A relationship between the prehydrolysis time of the silica precursor and the size of the niobia building blocks was observed. When 1,2-bis(triethoxysilyl)ethane was first hydrolyzed for 30 min before adding niobium penta-ethoxide, the niobia building blocks reached a radius of 0.4 nm. Simultaneous hydrolysis of the two precursors resulted in somewhat larger average building block radii of 0.5-0.6 nm. This study shows that acid-catalyzed sol-gel polymerization of mixed hybrid silica niobium alkoxides can be rationalized and optimized by monitoring the structural evolution using time-resolved SAXS.

Time-resolved small angle X-ray scattering study of sol-gel precursor solutions of lead zirconate titanate and zirconia.

The evolution of nanostructure in sol-gel derived lead zirconate titanate (PZT) and zirconia precursor sols at different hydrolysis ratios was investigated by small angle X-ray scattering (SAXS). The shape of the clusters in the zirconia sol could be described by the length-polydisperse cylindrical form factor. The zirconia-based clusters were characterized by a cross-sectional radius, r(0), of 0.28 nm and a practically monodisperse length of ca. 1.85 nm. These clusters were probably constructed of zirconia-related tetrameric building blocks. Similar cylindrical structural motifs were observed in PZT precursor sols with [H(2)O]/[Zr+Ti]=9.26 and 27.6, but the polydispersity in length was much higher. Clear scattering contributions from Ti and Pb centers were not detected, which was interpreted in terms of a homogeneous distribution of unbound lead ions in solution and the relatively low scattering intensity from any Ti-based clusters or oligomers that may have been present in the sols.

Development of nanoscale inhomogeneities during drying of sol-gel derived amorphous lead zirconate titanate precursor thin films.

The structural evolution of sol-gel derived lead zirconate titanate (PZT) precursor films during and after physical drying was investigated by transmission electron microscopy (TEM), electron energy loss spectroscopy (EELS), selected area electron diffraction (SAED), and time-resolved X-ray diffraction (XRD). Films were deposited from initial 0.3 mol/dm(3) precursor sols with varying hydrolysis ratios. Zr-rich grains of 1-10 nm size, embedded in a Pb-, Zr-, and Ti-containing amorphous matrix were found in as-dried films. The Zr-rich regions were crystalline at hydrolysis ratios [H(2)O]/[PZT] < 27.6, and amorphous at ratios > 100. X-ray diffraction analysis of PZT and zirconia sols revealed that the crystalline nanoparticles in both sols are identical and are probably composed of nanosized zirconium oxoacetate-like clusters. This study demonstrates that time-resolved X-ray diffraction combined with electron energy loss spectroscopy mapping is a powerful tool to monitor the nanoscale structural evolution of sol-gel derived thin films.

Studies of water and ice in hydrophilic and hydrophobic mesoporous silicas: pore characterisation and phase transformations.

A study has been made as a function of temperature of the phase transformation of water and ice in two samples of mesoporous silica gel with pore diameters of approximately 50 A. One sample was modified by coating with a layer of trimethylchlorosilane, giving a predominantly hydrophobic internal surface, whereas the unmodified sample has a hydrophilic interface. The pore structure was characterised by nitrogen gas adsorption and NMR cryoporometry and the melting/freezing behaviour of water and ice in the pores was studied by DSC and neutron diffraction for cooling and heating cycles, covering a range of 200 to 300 K. Measurements were made for several filling-factors in the range 0.2 to 0.9. The results show a systematic difference in the form of ice created in each of the samples. The non-modified sample gives similar results to previous studies with hydrophilic silicas, exhibiting a defective form of cubic ice superimposed on a more disordered pattern that changes with temperature and has been characterised as 'plastic' ice [Liu et al., 2006, Webber et al., 2007]. The modified sample has similar general features but displays important variability in the ice transformation features, particularly for the case of the low filling-factor (f = 0.2). The results exhibit a complex temperature-dependent variation of the crystalline and disordered components that are substantially altered for the different filling-factors.

[Introduction of vaccination against human papillomavirus in developing countries: update and perspectives]. / Introduction de la vaccination contre les papillomavirus humains dans les pays en développement: bilan et perspectives.

Cervical cancer and other diseases related to human papillomavirus (HPV) represent a global public health problem. Safe and effective vaccines are now available and already used in many industrialized countries. Immunization offers the best hope for protecting the population against a disease that is the second most deadly cancer in the developing world and the first most deadly in Africa. The World Health Organization currently recommends introduction of HVP vaccination in developing countries. Widespread vaccination could be beneficial in numerous domains other than primary prevention of cervical cancer. Efforts to overcome the numerous obstacles and speed up implementation of HVP vaccination programs are now underway in many areas ranging from related scientific issues such as epidemiology and clinical research to administrative concerns such as healthcare economics, vaccination guidelines, public acceptation, program funding, and universal access. Vaccine manufacturers have committed themselves to working in partnership with national and international organizations to ensure access to HPV vaccine for all countries regardless of economic level, Although numerous issues must be resolved to optimize the use of HPV vaccines and ensure synergistic integration of vaccination, screening and treatment, current initiatives and efforts should allow introduction of HPV vaccination in developing countries in a not too distant future.

Stable hybrid silica nanosieve membranes for the dehydration of lower alcohols.

A thirst for water: Organic-inorganic hybrid silica nanosieve membranes with narrow pore size distributions were developed for the separation of binary (bio)alcohol/water mixtures, for example, to remove water from wet biofuels during production. These membranes dehydrate lower alcohols and show a stable performance in the presence of significant amounts of acetic acid.

Hybrid ceramic nanosieves: stabilizing nanopores with organic links.

Unprecedented hydrothermal stability in functional membranes has been obtained with hybrid organic-inorganic nanoporous materials, enabling long-term application in energy-efficient molecular separation, including dehydration up to at least 150 degrees C.

Highly mixed phases in ball-milled Cu/ZnO catalysts: an EXAFS and XANES study.

New highly mixed phases have been identified in Cu/ZnO systems by EXAFS and XANES at both the Cu and Zn K-edge. The phases were generated by ball-milling Cu(2)O/ZnO mixtures under three different atmospheres of synthetic air (SA), SA + CO(2) and CO(2). The system milled in CO(2) shows disproportionation of Cu(2)O into Cu(0), Cu(1+) (cuprite Cu(2)O-type phase) and Cu(2+) (tenorite CuO-type phase), while most of the Zn(2+) is transformed into a nanocrystalline/amorphous ZnO-type zincite that forms a superficial mixture of oxide and carbonate phases. When synthetic air is added to the CO(2) atmosphere, ball milling results in the oxidation of nearly half the Cu(1+) into Cu(2+) with no Cu metal formed. The copper phase in this material is almost entirely amorphous. In SA, a significant amount of Cu(2+)- and Zn(2+)-based phases appears to react to form a nanocrystalline/amorphous Cu(1-x)Zn(x)O (x approximately 0.3) solid solution. This distorted rock saltlike solid solution, in which Zn and Cu feature different octahedral environments, was never reported before. It is thought to be formed by incorporation of Zn(2+) in the Cu fcc sublattice of the cuprite Cu(2)O matrix and the concomitant oxidation of Cu(1+) into Cu(2+). The formation of such a highly mixed Cu(1-x)Zn(x)O phase indicates strong Cu/Zn interaction in the Cu/ZnO system, which also suggests the presence of highly mixed phases in conventionally prepared activated catalysts.

Impact of osmolality on burning sensations during and immediately after intramuscular injection of 0.5 ml of vaccine suspensions in healthy adults.

A randomised placebo controlled double-blind cross-over trial was performed on twenty healthy adults to assess the effect of osmolality (300,600,850 and 1100 mOsm) on local tolerance of an intramuscular injection (0.5 ml) of five suspensions containing the same components as the excipients of a combined Diphtheria-Tetanus-acellular Pertussis-inactivated Poliomyelitis-Haemophilus influenzae type b paediatric vaccine (DtacP-IPV-Hib, PENTAVAC). The results did not show any dose-effect relationship between burning or pain sensations and the different osmolalities tested. Although mild and not clinically relevant, these sensations seemed to occur more frequently following injection of an isotonic saline solution (P<0.05). Thus, the osmolality of vaccine like suspensions does not appear to be a potential cause of local pain or burning sensation after their administration.

Immunogenicity and safety of a new liquid hexavalent combined vaccine compared with separate administration of reference licensed vaccines in infants.

OBJECTIVE: The immunogenicity and safety of a new liquid hexavalent vaccine (diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-hepatitis B-polyribosyl ribitol phosphate conjugated to tetanus protein; Hexavac; Aventis Pasteur MSD, Lyon, France) are compared with those of reference vaccines [diphtheria-tetanus-acellular pertussis-inactivated polio vaccine reconstituting lyophilized purified Haemophilus influenzae polysaccharide conjugated to tetanus protein vaccine (Pentavac; Aventis Pasteur MSD) and hepatitis B vaccine (H-B-Vax II; Aventis Pasteur MSD)] injected separately at the same visit in a prospective multicenter, comparative, open label trial. METHODS: Infants were randomized to receive Hexavac (n = 423) or Pentavac and H-B-Vax II (n = 425) as a primary immunization series at 2, 4 and 6 months of age. Seroprotection and seroconversion rates against all antigens at 1 month after the primary series were compared between the two vaccine groups with 95% confidence intervals (CI0.95) and were considered clinically equivalent (not inferior) when the upper limit of the 95% confidence interval on the difference (reference, hexavalent) was below predefined differences. RESULTS: Hexavac met and surpassed the pre-defined criteria for clinical equivalence to Pentavac and H-B-Vax II given concomitantly. It elicited similar seroprotection and seroconversion rates against all antigens. Seroprotection and seroconversion rates obtained 1 month after the third dose of Hexavac were >90% for all antigens. The postimmunization antibody geometric mean titers (GMT) for hepatitis B and purified Haemophilus influenzae polysaccharide were about 2-fold higher in infants who received the reference vaccines than in infants who had received Hexavac. GMTs for poliovirus antibodies tended to be enhanced in infants vaccinated with Hexavac. GMTs for all other antigens were very similar among both groups. Hexavac was generally well-tolerated. At least one local reaction was reported in 20.3% of Hexavac injections compared with 15.8% at the Pentavac injections site and 3.8% at the H-B-Vax II injections site. These reactions were generally mild and transient. At least one systemic adverse event was reported in 45.7% of Hexavac injections compared with 42.2% of Pentavac and H-B-Vax II injections (mild fever, irritability and drowsiness were most frequently reported). The frequency of adverse events was not significantly different between groups. No vaccine-related serious adverse event occurred during the study. CONCLUSION: This liquid hexavalent vaccine was generally well-tolerated and provided immune responses adequate to be protective against six infectious diseases with a single injection, given at 2, 4 and 6 months of age.

Experience with Salmonella typhi Vi capsular polysaccharide vaccine.

Typhoid fever remains an important health threat in many parts of the world, with an estimated 16 million cases and 600,000 deaths occurring each year. The emergence of Salmonella typhi strains multiply resistant to antibiotics has complicated the treatment of this disease. Field experience of 8 years shows that a vaccine composed of purified Vi capsular polysaccharide of Salmonella typhi, given as a single intramuscular or deep subcutaneous injection, has consistent immunogenicity and efficacy. Side effects, based on reports since 1989, are infrequent and mild. Furthermore, the Vi vaccine may be administered simultaneously with other common "travel" vaccines, at two different sites of injection, without affecting immunogenicity and tolerability. This review presents an update of the development and clinical experience with the Salmonella typhi Vi polysaccharide vaccine (Typhim Vi; Pasteur Mérieux Connaught, France).

The immunogenicity and safety of a new combined diphtheria, tetanus and poliomyelitis booster vaccine (Td-eIPV).

In view of the continuing risk of contracting tetanus, diphtheria and poliomyelitis, and the well-documented decline in immunity with time, the need for booster vaccinations is substantial. The immunogenicity and safety of a new combined booster vaccine against tetanus, diphtheria and poliomyelitis (REVAXIS) developed by Pasteur Mérieux Connaught (Lyon, France) were evaluated in four clinical studies. This vaccine (Td-eIPV) combines an adsorbed tetanus toxoid and low-dose diphtheria toxoid vaccine (Td) with an enhanced, inactivated polio vaccine against poliovirus types 1, 2 and 3 (eIPV). In 256 healthy young adults, a single dose of Td-eIPV was shown to be immunogenic, eliciting antibody levels considered protective against disease for each vaccine component in > or = 99.6% of the subjects. In 112 healthy older subjects (> 40 years of age), two doses of Td-eIPV elicited seroprotective levels of antibodies in 94% of the subjects for diphtheria, and in all subjects for tetanus and poliovirus types 1, 2 and 3. Safety data from all 368 subjects, as well as 31 phase I volunteers and 1,742 subjects included in a safety study, reveal that the vaccine is safe. Most reactions were predictable, temporary and mild. There was no evidence that the vaccine was associated with any clinically serious event or modification of clinical laboratory parameters. The data reviewed here show that Td-eIPV is immunogenic and safe when administered as a booster vaccination in healthy adults of all ages.

[Efficacy of pneumococcal vaccination]. / Efficacité de la vaccination pneumococcique.

POLYVALENT VACCINE: Pneumococcal vaccination is based on the antigenic properties of polysides carried on the bacterial capsule which induce production of bactericidal serotype-specific antibodies. The 23 serotypes contained in the current vaccine cover 85 to 90% of all strains observed in pneumococcal infections in Europe. PROVEN EFFICACY: Prospective and retrospective studies have demonstrated that pneumococcal vaccination can prevent 60 to 80% of invasive pneumococcal infections in immunocompetent elderly subjects and/or persons in high-risk groups with underlying disorders. TARGET POPULATION: Immunocompetent persons in the 60-65 year and older age group comprise the target population for pneumococcal vaccination. Incidence and mortality of pneumococcal infections is high in this group. Simple vaccination strategies should be implemented.

Human diploid cell strains (HDCS) viral vaccines.

Since the development in 1961 by Hayflick and Moorhead of a human diploid cell strain (HDCS) culture system for isolating viruses, HDCS-derived human vaccines have been licensed worldwide for polio IPV and OPV (multiple strains), rabies (Pitman-Moore L503 3M strain); rubella (RA27/3 strain); measles (Edmonston-Zagreb strain); varicella-zoster (Oka strain); mumps (Rubini strain) and hepatitis A (HM-175, CR-326-F', and GBM strains). Many of these widely-used vaccines now have at least a 20-year record of safety after extensive, ongoing pharmacovigilance. Serious vaccine-associated events are rare, and appear to reflect the activity of the live viruses replicated in the HDCS or of the inactivated viruses or other proteins added during manufacture. There is no credible association of reactions to the HDCS substrate or a hypothetical contaminant derived from it.

[Aseptic meningitis after mumps vaccination]. / Méningites aseptiques après vaccination anti-ourlienne.

The aim of this retrospective study was to evaluate the incidence and the characteristics of spontaneously reported aseptic meningitis (AM) in France following mumps vaccination with monovalent or multivalent vaccines containing the Urabe strain. Fifty-four cases of AM were reported to the regional drug surveillance centres or to the manufacturer from the time each vaccine was launched up until June 1992. Twenty cases were associated with the time off administration of a monovalent mumps vaccine and 34 with a trivalent measles, mumps and rubella vaccine (MMR). A mumps virus was isolated in four cases in the cerebrospinal fluid and an Urabe-like strain was characterised twice by polymerase chain reaction (PCR). A probable mumps origin was assumed in 17 other cases where the patients presented with other clinical or biological signs of mumps infection. The clinical outcome of AM was always favourable. The global incidence of mumps vaccine-associated AM was 0.82/100,000 doses, which is significantly lower than the incidence in the unvaccinated population. Even considering that the actual incidence of AM is much higher when assessed by active surveillance studies, the risk/benefit ratio of mumps vaccine remains in favour of vaccination. The incidence of mumps vaccines containing Jeryl Lynn (ROR Vax et Imu ORR) associated with AM needs to be evaluated.

[Thrombocytopenic purpura after isolated or combined vaccination against measles, mumps and rubella]. / Purpura thrombopénique après vaccination isolée ou associée contre la rougeole, la rubéole et les oreillons.

A retrospective epidemiological survey was conducted to evaluate the incidence and characteristics of thrombocytopenic purpura (TP) reported in France following measles, mumps or rubella vaccination with monovalent or multivalent vaccines. Sixty cases of TP were reported i.e an incidence/100,000 doses of 0.23 and 0.17 for measles or rubella vaccines respectively given alone, to 0.87 for combined measles-rubella vaccine and 0.95 for MMR vaccine. The mean age was 21 +/- 12 months and the delay of diagnosis was 16 +/- 6 days after vaccination. Thrombopenia was severe (mean platelet count: 8000 +/- 6000/mm3) and always associated with purpura. The immediate outcome was favourable in 89.5 per cent of cases. Vaccine-associated TP appears to be similar to acute childhood idiopathic thrombocytopenic purpura but the clear temporal relationship between MMR vaccination and the occurrence of TP make a causal relationship highly plausible. Acute TP seems a rare complication of measles-rubella and MMR vaccination but clinicians had to be informed of the possibility of their occurrence. Acute TP following vaccination should be reported by physicians to their Regional Drug Surveillance Centre.