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Biomedical subjects

N Guérin

Publications and source records attributed to N Guérin.

At least 19 recordsLinked to original sources

[French survey about intradermal BCG SSI adverse events in children under 6 years of age].

During April 2006, 579 physicians took part in a survey about intradermal BCG SSI adverse events (AE) in children less than 6 years old, managed by InfoVac France. Since January 2006, 68% physicians (paediatricians: 73% and general practitioners [GP]: 60%) have vaccinated at least one child. The site of injection is mainly the extern side of the shoulder (72%), according to the recommendations. Systematic vaccination is continued by 54% GP and 26% paediatricians. Others indications are: admission in day care center (33%), admission in day care center associated with risk factors (24%), or only risks factors (8%). Half physicians observed AE and 6% of them reported them at pharmacovigilance centers or pharmaceutical company. AE were mainly inflammations or indurations over 1 cm (for 75% of physicians who observed AE), oozing (73%). Abscesses are notified by 54%, ulcers by 39%, lymphadenopathies over 1 cm by 20%, suppurative lymphadenopathies by 3% and keloid scares by 17% of them, several AE may coexist for some children. Our aim is to start a prospective follow-up of BCG-SSI vaccination and its AE; 58% physicians who answered this investigation agreed to participate.

Adverse Drug Reaction Reporting Systems↗

[Vaccinations for traveler child].

Each year, half a million of children leave France to travel towards countries south or east of the European Union, sometimes in poor sanitary conditions. In order to propose essential or useful immunizations for these trips, the current synthesis will allow the practitioner to insure that the routine French immunization schedule has been followed, and to complete it if needed, to protect the child according to the epidemiological situation in the visited area, to try to reduce the limitations of the immunization of the traveler child. In case of emergency, or close departure, it may be useful to follow an accelerated schedule of the last minute, and, sometimes, to immunize traveler children with a chronic disease. Informations on Internet sites useful for the knowledge of current infectious risks in the destination country are also provided.

France↗

[History of vaccination: from empiricism towards recombinant vaccines].

PURPOSE: Two hundreds years after the discovery of the smallpox vaccine, immunization remains one of the most powerful tools of preventive medicine. CURRENT KNOWLEDGE AND KEY POINTS: Immunization was born with Jenner, then Pasteur and expanded during the 19th and 20th century. It started with the empirical observation of cross-immunity between two diseases, cowpox and smallpox. It became a real science, with pathogen isolation, culture and attenuation or inactivation, to prepare a vaccine. Together with clinical and biological efficacy studies and adverse events assessments, it constructed the concept of "vaccinology". Protein conjugation of polyosidic vaccines has made possible early immunisation of infants. Nowadays, recombinant, reassortant, or virus-like particles technologies open the road for new vaccines. FUTURE PROSPECTS: Ongoing research opens the way for the development of new vaccines that will help to control transmittable diseases for which we are lacking antimicrobial agents.

Empirical Research↗

[Action to be taken when facing one or more cases of whooping-cough].

The evolution of the epidemiology of pertussis, new licensed macrolides and vaccines, new recommendations for vaccination among adolescents and adults need an update of the French guidelines for prevention of the disease around one or grouped cases of the disease. A particular attention should be raised to the diagnosis of whooping cough in adults who are presently the main reservoir of Bordetella pertussis. Whooping cough in adults presents as an unexplained prolonged cough with nocturnal exacerbation witch accounts for most of the contaminations of young infants. A bacteriological confirmation of pertussis should be provided before implementation of preventive measures: culture and PCR are presently the gold standard for the diagnosis of pertussis in infants, children and even adults who have been coughing for less than 20 days. Later on, serology (Elisa, immuno-empreinte) is the only technique available, but cannot be interpreted if the patient has been vaccinated less than one year ago. Infants under three months should be admitted to hospital and every case submitted to respiratory isolation. Eviction from the community should be pronounced within the five first days following the onset of an effective antibiotic treatment. New macrolides should be favoured: clarithromycin for seven days or azithromycin for five days. Household contacts should be given the same prophylactic antibiotic treatment: children and adolescent not correctly immunized, parents of the index case as adults parents of not or not completely immunized infants. The vaccination program of the household should be updated. The same measures should be applied in case of grouped cases (at least two contemporary or consecutive cases in the same area). In that case, the Public Health System doctors should be involved in the investigation and the classification of the cases. The close contacts not or not completely immunized should be prescribed and antibiotic prophylaxis and an update of their vaccination program. Among the occasional contacts, high-risk people only should be treated. In the day care centres an antibiotic prophylaxis should be given to children who have received less than four vaccine shots against pertussis and to the personnel contact to the cases as well. In the schools, the antibiotic prophylaxis should be prescribed to all children of the classroom(s) not completely vaccinated and to the teacher(s) as well. In the boarding schools and institutions with handicapped children, antibiotic prophylaxis could be applied to every member if the pertussis vaccine coverage is at less than 50%. In hospitals, coughing personnel should wear masks and investigations towards pertussis should be performed in people with a more than seven day unexplained cough. Preventive measures should be applied in case of confirmation of pertussis.

Adult↗

Impairment in clock-time estimation following right hemisphere ischemic damage.

In order to assess clock-time estimation (CTE), we asked "what time is it in your opinion?" to 48 recent stroke in-patients, 21 with right (RH), 27 with left hemispheric (LH) lesions, and to 20 control in-patients without brain lesions (C). Errors were measured in terms of the number of minutes by which the estimated clock-time was later (advance errors) or earlier (delay errors) than the real clock-time. CTE was considered pathological when exceeding the mean advance or delay errors observed in control patients plus 2.5 standard deviations. The estimation of the duration of a short psychological interview was also assessed. CTE, and not duration estimation, was disturbed in patients. RH patients made significantly more pathological advance errors than LH patients (43% vs. 12%). This study points out the RH dominance for CTE in stroke patients.

Adult↗

Prevalence and trends of infection with Mycobacterium tuberculosis in Djibouti, testing an alternative method.

SETTING: Djibouti, 1994 and 2001. OBJECTIVE: To estimate the prevalence of tuberculosis (TB) and average annual risk of TB infection (ARTI) and trends, and to test a new method for calculations. METHODS: Tuberculin surveys among schoolchildren and sputum smear-positive TB patients. Prevalence of infection was calculated using cut-off points, the mirror image technique, mixture analysis, and a new method based on the operating characteristics of the tuberculin test. Test sensitivity was derived from tuberculin reactions among TB patients and test specificity from a comparison of reaction size distributions among children with and without a BCG scar. RESULTS: The ARTI was estimated to lie between 2.6% and 3.1%, with no significant changes between 1994 and 2001. The close match of the distributions between children tested in 1994 and patients justifies the utilisation of the latter to determine test sensitivity. This new method gave very consistent estimates of prevalence of infection for any induration for values between 15 and 20 mm. Specificity was successfully determined for 1994, but not for 2001. Mixture analysis confirmed the estimates obtained with the new method. CONCLUSION: Djibouti has a high ARTI, and no apparent change over the observation time was found. Using operating test characteristics to estimate prevalence of infection looks promising.

Bayes Theorem↗

[Updating immunization schedules in France].

Complete updating of the immunization schedules can be a major problem in children arriving in France from developing countries either to join their families or to be adopted. It is necessary to determine which vaccinations have already been administered prior to arrival in France and if necessary complete the schedule in accordance with the French immunization schedule. In case of doubt or difficulty in reading or interpreting records, it may be helpful to obtain a translation or consult the prevailing immunization schedule in the country of origin. In case of doubt about the quality of previous vaccination due to missing immunization records, the child should be considered as exposed and undergo vaccination. For vaccination requiring a series of injections, circulating antibodies should be measured after the first dose. The series should be completed only if results show a primary reaction. This approach avoids administration of unnecessary doses.

Adolescent↗

[Efficacy and tolerance of vaccinations in premature infants].

Immunization may prevent an enhanced risk of infectious diseases, providing that it is completed on time. A review of the literature summarizes several studies on effectiveness, safety and duration of protection in preterm infants. Immune maturation depends on chronological age rather than gestational age. Then immunization against diphteria-tetanus-pertussis-poliomyelitis-Haemophilus influenzae b should be initiated at 2 months of age and completed prior than 6 months. The youngest preterm infants, still hospitalized at 8 weeks of age should be monitored following the first immunization as they may develop apnea episodes, probably linked with the pertussis component of the vaccine. In premature, BCG vaccination induces a delayed hypersensitivity to tuberculin less important than in full-term neonates, and should not be given right after birth in newborns less than 33 weeks of gestational age. Hepatitis B vaccination should be offered as soon as two months of age and even at birth to children born from HBs Ag carriers. Neither duration of immunity, nor safety are modified by prematurity.

Age Factors↗

Altered organ accumulation of oligonucleotides using polyethyleneimine grafted with poly(ethylene oxide) or pluronic as carriers.

Passive targeting provides a simple strategy based on natural properties of the carriers to deliver DNA molecules to desired compartments. Polyethylenimine (PEI) is a potent non-viral system that has been known to deliver efficiently both plasmids and oligonucleotides (ODNs) in vitro. However, in vivo systemic administration of DNA/PEI complexes has encountered significant difficulties because these complexes are toxic and have low biodistribution in target tissues. This study evaluates PEI grafted with poly(ethylene oxide) (PEO(8K)-g-PEI(2K)) and PEI grafted with non-ionic amphiphilic block copolymer, Pluronic P85 (P85-g-PEI(2K)) as carriers for systemic delivery of ODNs. Following i.v. injection an antisense ODN formulated with PEO(8K)-g-PEI(2K) accumulated mainly in kidneys, while the same ODN formulated with P85-g-PEI(2K) was found almost exclusively in the liver. Furthermore, in the case of the animals injected with the P85-g-PEI(2K)-based complexes most of the ODN was found in hepatocytes, while only a minor portion of ODN was found in the lymphocyte/monocyte populations. The results of this study suggest that formulating ODN with PEO(8K)-g-PEI(2K) and P85-g-PEI(2K) carriers allows targeting of the ODN to the liver or kidneys, respectively. The variation in the tissue distribution of ODN observed with the two carriers is probably due to the different hydrophilic-lipophilic balance of the polyether chains grafted to PEI in these molecules. Therefore, polyether-grafted PEI carriers provide a simple way to enhance ODN accumulation in a desired compartment without the need of a specific targeting moiety.

Animals↗

Role of school schedule, age, and parental socioeconomic status on sleep duration and sleepiness of Parisian children.

The aim of the study was to assess the duration and quality of sleep of prepubertal (Tanner Scale level 1) physically and mentally healthy children as a function of school schedule (4 versus 4.5 days per week), age and grade (median age of 9.5 years for 4th grade versus median age of 10.5 years for 5th grade), school district (wealthy versus nonwealthy) in Paris, France, and parental socioeconomic status (high, medium, or low). We studied 51 girl and 44 boy volunteer pupils with written parental consent. The study lasted 2 weeks during the month of March. During the first study week, the children attended school 4.5 days, and during the second week, they attended school only 4 days without difference in the length of the school day. A sleep log was used to ascertain time of lights off for sleep and lights on at awakening, nighttime sleep duration, and self-rated sleep quality. A visual analog scale (VAS) was also used by pupils to self-rate the level of perceived sleepiness at four specific times of the school day. Conventional statistical methods (e.g., t and chi2 tests) were used to examine differences in mean values. Sleep duration, self-rated sleepiness, and subjective sleep quality were comparable (P > .05) by gender, school schedule, school district, and parental socioeconomic status. Overall, the sleep of this sample of Parisian children around 10 years of age was rather stable in its duration and timing, suggesting flexibility to adjust to the different school schedules.

Age Factors↗

The use of smallpox virus as a biological weapon: the vaccination situation in France.

In the context of its plan to fight against bioterrorism, the Ministry of Health asked the Institut de Veille Sanitaire to evaluate the epidemic risk from a release of the small pox virus, and to make recommendations on potential vaccination strategies to be implemented. A benefit/risk assessment of various vaccination scenarios, including vaccination of the whole French population, was carried out to evaluate the severity of a terrorist action threat. This analysis concludes that at this stage, vaccination action does not seem to be justified. Even in the case of a real threat, the vaccination of frontline healthcare personnel, and in particular of contacts of cases, must be given priority.

Age Factors↗

Evaluation of polyether-polyethyleneimine graft copolymers as gene transfer agents.

Cationic copolymers consisting of polycations linked to non-ionic polymers are evaluated as non-viral gene delivery systems. These copolymers are known to produce soluble complexes with DNA, but only a few studies have characterized the transfection activity of these complexes. This work reports the synthesis and characterization of a series of cationic copolymers obtained by grafting the polyethyleneimine (PEI) with non-ionic polyethers, poly (ethylene oxide) (PEO) or Pluronic 123 (P123). The PEO-PEI conjugates differ in the molecular mass of PEI (2 kDa and 25 kDa) and the degree of modification of PEI with PEO. All of these conjugates form complexes upon mixing with plasmids, which are stable in aqueous dispersion for several days. The sizes of the particles formed in these systems vary from 70 to 200 nm depending on the composition of the complex. However, transfection activity of these systems is much lower than that of PEI (25 kDa) or Superfect as assessed in in vitro transfection experiments utilizing a luciferase reporter expression in Cos-7 cells as a model system. In contrast, conjugate of P123 with PEI (2 kDa) mixed with free P123 (9:1(wt)) forms small and stable complexes with DNA (110 nm) that exhibit high transfection activity in vitro. Furthermore, gene expression is observed in spleen, heart, lungs and liver 24 h after i.v. injection of this complex in mice. Compared to 1,2-bis(oleoyloxy)-(trimethylammonio) propane:cholesterol (DOTAP:Chol) and PEI (25 kDa) transfection systems, the P123-PEI system reveals a more uniform distribution of gene expression between these organs, allowing a significant improvement of gene expression in liver.

Animals↗

A combination of poloxamers increases gene expression of plasmid DNA in skeletal muscle.

Intramuscular administration of plasmid DNA is a promising strategy to express therapeutic genes, however, it is limited by a relatively low level of gene expression. We report here that a non-ionic carrier, SP1017, composed of two amphiphilic block copolymers, pluronics L61 and F127, also known as poloxamers, significantly increases intramuscular expression of plasmid DNA. Two reporter genes, luciferase and beta-galactosidase, and one therapeutic gene, erythropoietin, were injected intramuscularly with and without SP1017 into C57Bl/6 and Balb/C mice and Sprague-Dawley rats. SP1017 increased gene expression by about 10-fold and maintained higher gene expression compared with naked DNA. Comparison of SP1017 with polyvinyl pyrrolidone (PVP) showed that SP1017 exhibited a significantly higher efficacy and its optimal dose was 500-fold lower. Experiments with beta-galactosidase using X-gal staining suggested that SP1017 considerably increased plasmid DNA diffusion through the tissue. SP1017 also improved expression of the erythropoietin gene leading to an increase in its systemic level and hematocrits. Previous toxicity studies have suggested that SP1017 has over a 1000-fold safety margin. Poloxamers used in SP1017 are listed in the US Pharmacopeia as inactive excipients and are widely used in a variety of clinical applications. We believe that the described system constitutes a simple and efficient gene transfer method to achieve local or systemic production of therapeutic proteins.

Animals↗

Block and graft copolymers and NanoGel copolymer networks for DNA delivery into cell.

Self-assembling complexes from nucleic acids and synthetic polymers are evaluated for plasmid and oligonucleotide (oligo) delivery. Polycations having linear, branched, dendritic. block- or graft copolymer architectures are used in these studies. All these molecules bind to nucleic acids due to formation of cooperative systems of salt bonds between the cationic groups of the polycation and phosphate groups of the DNA. To improve solubility of the DNA/polycation complexes, cationic block and graft copolymers containing segments from polycations and non-ionic soluble polymers, for example, poly(ethylene oxide) (PEO) were developed. Binding of these copolymers with short DNA chains, such as oligos, results in formation of species containing hydrophobic sites from neutralized DNA polycation complex and hydrophilic sites from PEO. These species spontaneously associate into polyion complex micelles with a hydrophobic core from neutralized polyions and a hydrophilic shell from PEO. Such complexes are very small (10-40 nm) and stable in solution despite complete neutralization of charge. They reveal significant activity with oligos in vitro and in vivo. Binding of cationic copolymers to plasmid DNA forms larger (70-200 nm) complexes. which are practically inactive in cell transfection studies. It is likely that PEO prevents binding of these complexes with the cell membranes ("stealth effect"). However attaching specific ligands to the PEO-corona can produce complexes, which are both stable in solution and bind to target cells. The most efficient complexes were obtained when PEO in the cationic copolymer was replaced with membrane-active PEO-b-poly(propylene oxide)-b-PEO molecules (Pluronic 123). Such complexes exhibited elevated levels of transgene expression in liver following systemic administration in mice. To increase stability of the complexes, NanoGel carriers were developed that represent small hydrogel particles synthesized by cross-linking of PEI with double end activated PEO using an emulsification/solvent evaporation technique. Oligos are immobilized by mixing with NanoGel suspension, which results in the formation of small particles (80 nm). Oligos incorporated in NanoGel are able to reach targets within the cell and suppress gene expression in a sequence-specific fashion. Further. loaded NanoGel particles cross-polarized monolayers of intestinal cells (Caco-2) suggesting potential usefulness of these systems for oral administration of oligos. In conclusion the approaches using polycations for gene delivery for the design of gene transfer complexes that exhibit a very broad range of physicochemical and biological properties, which is essential for design of a new generation of more effective non-viral gene delivery systems.

Cations↗

Comparison of the safety and immunogenicity of the lyophilized Mérieux seed and the World Health Organization working reference BCG vaccines in school-aged children in Senegal.

In order to validate two new lots of Mérieux BCG vaccine (Mérieux seed derived from strain 1072), a calibration study was performed to compare their safety and immunogenicity to a full dose of the WHO-reference BCG vaccine (Tokyo strain 172) as well as the WHO-reference vaccine given at 1/10 of its normal concentration, in an open, randomized, four-arm, multicenter study in Senegal. A total of 1041 healthy Senegalese children aged 8-10 years were screened for participation in this study, of whom 548 had a negative Mantoux test and complied with inclusion and exclusion criteria. These children were randomly allocated a single dose of one of the following vaccines: full-dose Mérieux BCG vaccine (lot E0650); full-dose Mérieux BCG vaccine (lot E0624); full-dose WHO-reference vaccine (Tokyo strain 172); or 1/10 dose WHO-reference vaccine. A follow-up examination, including a tuberculin test, was performed 10-12 weeks after BCG vaccination for 465 (85%) children: 236 Mérieux BCG vaccine (117 lot E0650; 119 lot E0624); 115 full-dose WHO; 114 1/10 dose WHO. The percentage of subjects with a positive tuberculin test after vaccination was significantly lower (P < 0.001) in the 1/10 dose group (81.5%) compared to the other three groups (> 96%). The mean induration diameter was significantly smaller in subjects who received the low-dose of WHO vaccine compared to the others, according to analyses considering all subjects vaccinated, as well as only those subjects with a positive tuberculin test after vaccination. More children in the low-dose group did not have a vaccination scar, and the mean diameter of scars was smaller in this group. The rate of tuberculin reactions, the classification of reactions (Palmer and Edwards), and the characteristics of the vaccinal lesion were similar for the Mérieux BCG vaccines and the full-dose WHO-reference vaccine. All vaccines were safe, as evidenced by the absence of adenitis or suppurative adenitis during the course of the study. Results from this trial show that the two lots of Mérieux BCG vaccine behave equally as well as the full-dose WHO-reference BCG vaccine. The WHO-reference vaccine, given at 1/10 of its normal concentration was significantly less immunogenic, according to all parameters evaluated.

BCG Vaccine↗

Assessing immunization coverage: how and why?

Assessment of immunization coverage is an important part of evaluating an immunization programme and it is a useful aid in programme management and decision making. Coverage assessment should be carried out at the national and district levels. Routine methods currently used in EU countries vary and are not always accurate, and should be validated regularly by specific surveys.

France↗