[Orthopedic aspects of Distal Active Concept therapy applied in the mixed dentition. Comparative study with an untreated population]. / Aspects orthopédiques de la thérapeutique Dac appliquée a la denture mixte. Etude comparative avec une population non traitée.

Our present study compares the skeletal and dentoalveolar changes between 120 subjects in mixed dentition treated with "Distal Active Concept" therapy versus 157 untreated subjects of class II served as a control group. Upon considering the treated subjects, a highly significant difference of mandibular growth (p < or = 0.001) with an anticlockwise rotation is noticed. The comparisons done according to gender and facial divergence show that the linear measurements are greater in males than females but the vertical relations are identical. Moreover, when considering hypodivergent and normodivergent subjects, all cephalometric values are similar and when regarding treated or non treated subjects, a significant difference of vertical growth factors exists and prevails. After comparaison, results clarify the benefits of early treatment for Class II malocclusion when the skeletal imbalance is considerable as it causes a quick mandibular response and hence improving the facial harmony dramatically.

Plasmodium yoelii: identification of a gene encoding a putative ADP-ribosylation factor-1 GTPase-activating protein, PyAG1.

The PyAG1 gene, identified by the screening of a Plasmodium yoelii genomic DNA library with a rhoptry-specific Mab, encodes a protein with a zinc finger structure immediately followed by the consensus sequence of the Arf GAP catalytic site. The serum of mice immunized with the recombinant protein recognized specifically the rhoptries of the late infected erythrocytic stages. Blast analysis using the Genbank database gave the highest scores with four proteins presenting an Arf1 GAP activity. If presenting also this activity, the PyAG1 protein could be involved in the regulation of the secreted protein vesicular transport and, consequently, in the rhoptry biogenesis.

Student satisfaction with curriculum modifications in a French dental school.

Since 1994, important modifications have been implemented in the dental curriculum in France, and an additional year has been included in the dental curriculum. The 1st year has remained unchanged; it is common to both medical and dental schools and leads to a selection procedure of 1 in 10 dental students. In the new curriculum, the dental student is engaged in a 5-year programme in dental school (years 2 to 6), as opposed to 4 years in the former programme (years 2 to 5). Basically, this new curriculum emphasises research initiation, links with medical training and offers broader clinical experience. During the academic year 1998-1999, dental schools had 2 different types of students: the 4th year students belonging to the new programme along with the 5th year students in their final year of the old curriculum. Using a specially devised questionnaire, we investigated the students' perception of their respective training, their motivation and professional plans. At the Faculty of Odontology in Lyon, the new curriculum is perceived as an increased strain by the dental students.

Oral health status in 65-74 years old adults in France, 1995.

BACKGROUND: A study was carried out to assess the oral health status of the non-institutionalized population aged 65-74 years and living in the Rhône-Alpes region, France, in 1995. METHODS: The representative sample was composed of 603 subjects comprised of 41.5% of men of which 24.5% lived in rural areas--i.e. less than 2,000 inhabitants--and 75.5% of urban areas. The quota sample used was stratified by socio-economic status, residence and gender. Oral health was defined by dentate status, D (Decayed), M (Missing), F (Filled) components and DMFT components. Carious lesions, fillings, missing teeth were recorded using the World Health Organization criteria. An indicator of treatment need--the ratio of decayed teeth over decayed and filled teeth--D/D+F was used. RESULTS: The DMFT index at 65-74 years for the French population was 23.3 +/- 4.0. The dental condition of the study group in the Rhônes-Alpes region of France appears satisfactory considering the low percentage of untreated decayed teeth at 65-74 years old (17.4%) and the low rate of edentate people (16.3%). Gender, location and socio-economic variables in relation to the dental status were discussed. CONCLUSION: The relatively good oral health status of the senior citizens and the low rate of need for treatment of dental decay together with the level of oral care available provided a solid base for further development of a qualitative national dental care system.

In vitro susceptibility of African isolates of Plasmodium falciparum from Gabon to pyronaridine.

The in vitro activity of pyronaridine was evaluated against 62 isolates of Plasmodium falciparum from Libreville, Gabon using an isotopic, drug susceptibility microtest and was compared with amodiaquine, chloroquine, quinine, and halofantrine activities. The mean 50% inhibitory concentration (IC50) values of the 62 isolates from Gabon to pyronaridine was 3.0 nM (95% confidence interval [CI] = 2.1-3.9). Pyronaridine was less potent against chloroquine-resistant isolates than chloroquine-susceptible isolates but more potent than chloroquine against chloroquine-resistant parasites. The cut-off value for in vitro reduced susceptibility to pyronaridine was an IC50 > 15 nM. Two isolates (3%) showed an IC50 > 15 nM. A significant positive correlation was found between the activities of pyronaridine and chloroquine (r2 = 0.26, P < 0.001), pyronaridine and quinine (r2 = 0.36, P < 0.001), pyronaridine and amodiaquine (r2 = 0.55, P < 0.001), and pyronaridine and halofantrine (r2 = 0.50, P < 0.001). This correlation suggests in vitro cross-resistance or at least in vitro cross-susceptibility, which is not necessarily predictive of cross-resistance in vivo. The present in vitro findings require comparison with those of clinical studies.

Periodontal conditions in 65-74 year old adults in France, 1995.

In 1995, a study was undertaken in France to assess the periodontal health status of 603 noninstitutionalized elderly subjects aged 65-74 years. Thirty areas were identified in the Rhône-Alpes region, with a sampling method based on stratified quotas according to sex, place of residence and socio-economic group (S-EG). The CPITN index was used. The total prevalence of healthy dentate adults (n = 483) was 16.5 per cent, whilst 16.3 per cent of the adults were edentulous. The prevalence of CPITN code 1 + 2 (low) was 50.7. The higher S-EG having fewer codes 1 and 2 (45.8 per cent) than the lower S-EG (49.7 per cent) and the medium S-EG (55.7 per cent). The total prevalence of periodontal disease (code 3 + 4) was 31.5. The prevalence of periodontal disease was lower in adults of medium socio-economic status and was also lower in adults living in urban residences. Overall, 66.9 per cent of the entire population needed oral hygiene instruction, 56.6 per cent scaling and 2.3 per cent complex periodontal treatment.

Plasmodium yoelii: identification of rhoptry proteins using monoclonal antibodies.

Thirteen monoclonal antibodies, obtained after immunization of mice with Plasmodium yoelii schizonts, were selected using immunofluorescence assay: they all presented typical fluorescence patterns of rhoptries. This antigen localization was confirmed by immunoelectron microscopy. The molecular weights of the recognized antigens are 68, 80, 105, 130 and 140 kDa as determined by immunoprecipitation and immunoblot under reducing and nonreducing conditions. These values are very similar to these of the low and high molecular weight complex components of Plasmodium falciparum. Furthermore, these antigens are soluble like P. falciparum rhoptry proteins. Interestingly, our monoclonal antibodies also reacted with two other Plasmodium species (Plasmodium berghei NKK173 strain and P. yoelii nigeriensis 798 VK strain), giving sometimes more complex labeling with apical, membranous, nuclear, or/and cytoplasmic localizations. Finally, none of the monoclonal antibodies stained the rhoptries of P. falciparum FCCE-1/Niger strain.

Synthesis and antimalarial activities of fluoroalkyl derivatives of dihydroartemisinin.

Fluoroalkyl ethers (4) of dihydroartemisinin (2) have been prepared by reaction of fluoroalkyl alcohols with dihydroartemisinin by different methods (BF3,Et2O or TMSCl catalysis or Mitsunobu reaction). Ethers 4a-d derived from primary fluoroalkyl alcohols were obtained in moderate to good yields by these methods. Ethers 4e-j have been prepared from fluoroalkyl secondary and tertiary alcohols and phenol using the Mitsunobu reaction. Although in vitro antimalarial activities of ethers toward Plasmodium falciparum W-2 asiatic strain are moderate, in vivo activities against Plasmodium berghei (NT 173) are excellent.

In-vitro activity of pyronaridine and amodiaquine against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial agents.

The in-vitro activities of pyronaridine, amodiaquine, chloroquine and quinine were evaluated against 161 isolates of Plasmodium falciparum from Senegal (Dielmo, Ndiop and Pikine), using an isotopic, micro, drug susceptibility test. The mean IC50 values (50% inhibitory concentration) for pyronaridine and amodiaquine were 3.8 nM (95% confidence interval (95% CI), 3.1-4.4) and 12.0 nM (95% CI, 10.0-14.0 nM), respectively. Pyronaridine and amodiaquine were more active than chloroquine against susceptible parasites. However, both drugs were significantly less active (P < 0.002 and P < 0.025) against chloroquine-resistant isolates than against chloroquine-susceptible isolates. Based on statistical calculation using the present data (mean IC50 + 2 S.D.), the cut-off value for in-vitro susceptibility to pyronaridine is IC50 < 15 nM; for eight isolates (5%) the IC50 was > 15 nM. No isolates tested showed resistance to amodiaquine (IC50 > 80 nM). Significant positive correlations, suggesting cross-resistance among these drugs in vitro, were found between pyronaridine and chloroquine (r2 = 0.19, P < 0.001), pyronaridine and quinine (r2 = 0.44, P < 0.001), pyronaridine and amodiaquine (r2 = 0.34, P < 0.001), amodiaquine and chloroquine (r2 = 0.14, P < 0.001), and amodiaquine and quinine (r2 = 0.21, P < 0.001). The present in-vitro findings require comparison with clinical studies.

In vitro activity of artemether against African isolates (Senegal) of Plasmodium falciparum in comparison with standard antimalarial drugs.

The in vitro activity of artemether against 56 African isolates of Plasmodium falciparum from Senegal was evaluated using an isotope-based drug susceptibility semi-microtest. The 50% inhibitory concentration (IC50) values for artemether were in a narrow range from 0.8 to 15.2 nM (mean IC50 = 3.43 nM) and the 95% confidence interval (CI) was 2.50-4.36 nM. Artemether was equally effective on chloroquine-sensitive and chloroquine-resistant isolates (mean IC50 = 346 nM, 95% CI = 2.08-4.84 nM versus mean IC50 = 2.80 nM, 95% CI = 2.00-3.60 nM). There was a significant positive correlation between responses to artemether and mefloquine (r2 = 0.36, P < 0.001), artemether and quinine (r2 = 0.085, P < 0.05), artemether and halofantrine (r2 = 0.075, P < 0.05), quinine and mefloquine (r2 = 0.205, P < 0.01), quinine and halofantrine (r2 = 0.124, P < 0.05), and mefloquine and halofantrine (r2 = 0.801, P < 0.001). A positive correlation between these drugs suggests in vitro cross-resistance or at least in vitro cross-susceptibility.

In vitro susceptibility of Gabonese wild isolates of Plasmodium falciparum to artemether, and comparison with chloroquine, quinine, halofantrine and amodiaquine.

The in vitro activity of artemether against 63 African isolates of Plasmodium falciparum from Libreville, Gabon was evaluated using an isotopic drug susceptibility semi-microtest. The 50% inhibitory concentration (IC50) values for artemether were in a narrow range from 0.8 to 34.8 nM (mean IC50 5.0 nM) and the 95% confidence interval (CI95%) was 3.6-6.3 nM. In vitro decreased susceptibility or resistance were observed with artemether (14%), to chloroquine (90%), to quinine (32%). Isolate susceptibility to amodiaquine and halofantrine was high i.e. 100% and 98%, respectively. There was a significant positive correlation between responses to artemether and amodiaquine (r2 = 0.45, P < 0.001), artemether and chloroquine (r2 = 0.36, P < 0.001), artemether and quinine (r2 = 0.31, P < 0.001), and artemether and halofantrine (r2 = 0.19, P < 0.01). Positive correlation between these drugs suggests in vitro cross-resistance or at least common features in drug uptake and/or mode of action or resistance.

Periodontal conditions in 35-44-yr-old adults in France, 1993.

A national study was carried out in France in 1993 to assess the periodontal status of the population aged 35-44 yr. The study took part in the Second International Collaborative Study of Oral Health Outcomes developed and coordinated by the World Health Organization. The representative sample was composed of 1000 subjects. The Community Periodontal Index of Treatment Needs (CPITN) index was used. Gingivitis prevalence was high (80.4%) while 26.6% of dentate subjects had shallow pockets (4-5 mm). Deep pockets (> 6 mm) were rare (1.6%) concerning on average 0.1 sextant per subject; 87.5% of the 994 dentate adults needed periodontal treatment. Oral health education and scaling should reduce periodontal pathology in this population group.

Characterisation of the binding sites of monoclonal antibodies reacting with the Plasmodium falciparum rhoptry protein RhopH3.

Twenty one mouse monoclonal antibodies reacting or cross-reacting with the Plasmodium falciparum RhopH3 protein reacted with Ag44, a recombinant antigen expressing the 134 C-terminal RhopH3 residues. Using overlapping peptides scanning this region, two major binding sites were identified. The first one, recognised by eight anti-RhopH3 and seven cross-reacting mAbs, was mapped to the sequence Thr Asp Asn Thr Tyr or Thr Asp Asn Thr Tyr Lys (aa 823-828), depending on the support used for synthesis. Binding specificity and affinity were investigated for a subset of four mAbs reacting with this epitope, including one growth inhibitory mAb. Systematic replacements showed that the various mAbs had similar requirements. The inhibitory mAb presented a higher affinity for this sequence and bound to the adjacent sequence, Tyr Lys Glu Met Glu Leu (aa 827-832). A 2nd binding site, located around residue 850, was recognised by two anti-RhopH3 mAbs, which reacted exclusively with the 110 kDa RhopH3 polypeptide, unlike the other mAbs, which reacted with the 110 and 105 kDa RhopH3 antigens. This suggested that the 105 kDa RhopH3 polypeptide derives from the 110 kDa by C-terminal processing. Experimental evidence substantiating this conclusion was provided by the observation that antisera raised to peptides located upstream of the putative cleavage site reacted with both the 110 kDa and 105 kDa polypeptides, whereas antisera raised to the 45 C-terminal amino acids of RhopH3 reacted exclusively with the larger, 110 kDa product. The biological significance of this processing is discussed.

Oral health in 35-44 year old adults in France.

In 1994, a national study was carried out in the Rhône-Alpes area of France, within the WHO International Collaborative Study on Oral Health Outcomes. One thousand, 35-44-year-old adults were examined in 35 geographical sites. WHO assessment forms were used for the survey. None of the 35-44 year olds were edentulous and 97 per cent of the sample had more than 20 natural teeth present. The mean number of teeth was 27.1. The DMFT index was 14.6. The DT component was 1.2 and MT was 3.0. FT (10.4) was the major component of the DMFT index. Of the 1000 adults, 90.9 per cent did not have bridges, 48.8 per cent needed conservative treatment and 51.9 per cent required crowns or bridges. Indications for fillings were frequent and concerned on average one tooth per subject. Disparities are brought to the fore between dental health and the required treatment, and the following variables: gender, location and socio-economic status.

[Drug sensitivity of falciparum malaria imported into France in 1995]. / Chimiosensibilité du paludisme d'importation à Plasmodium falciparum en France en 1995.

The National Reference Centre for Malaria Chemosusceptibility (CNRCP) and the Tropical Medicine Institute of the Health Department for the Army (IMTSSA) monitor the chemosusceptibility of falciparum malaria introduced in France. In 1995, 353 isolates of P. falciparum are sent to the CNRCP and IMTSSA from malaria cases presenting in 49 civil and military hospitals distributed all over the french country. The patients are mostly Africans living in France and have mainly stayed in West Africa. Half of them did not take any chemoprophylaxis and a quarter took only chloroquine more or less regularly. The curative treatment, when known, is halofantrine alone in 52% of cases and quinine alone in 28% of cases. Three halofantrine failures are reported including 1 incorrect regimen and 4 quinine failures including 3 incorrect regimens. In 1995, in vitro resistance of P. falciparum isolates imported in France to the chemoprophylactic and therapeutic drugs is not worsening. In vitro quinine resistance is rare (1/108), mefloquine resistance (2/20) and halofantrine resistance (12/211) are limited, cycloguanil resistance (42/185) is stable and chloroquine resistance (84/230) is even decreasing (less selective pressure in Africa?).

[Malaria epidemic during a military-humanitarian mission in Africa]. / Epidémie de paludisme au cours d'une intervention militaro-humanitaire en Afrique.

A malaria epidemic broke out among French servicemen during a humanitarian military mission carried out in Central Africa in 1996. The purpose of this study was to determine compliance with drug prophylaxis for malaria by measuring blood levels of antimalarial drugs (combination treatment using chloroquine-proguanil or treatment with doxycycline) as well as to assess the conditions of vector control. The incidence density rate of malaria over a 60-day period was 3.1 cases per month per 100 men. Only reinforcement troops were affected. The risk of developing malaria was 5 times higher among new arrivals than in servicemen who had been in the zone for several months (95% CI relative risk = [2.9-7.8]). Type of prophylactic treatment had no effect on the incidence density rate. Study data showed that 40.2% of those treated for malaria were not in compliance with prophylactic treatment at the time of the malarial attack and that those who were in compliance with prophylaxis, i.e. the remaining 59.8%, presented a strain of plasmodium that was resistant to the prophylactic drugs at doses used. Findings also indicated the epidemic occurred mainly because operating conditions prevented implementation of proper vectorial control. The risk of epidemic could probably have been reduced by improving compliance with prophylactic treatment and changing standard vectorial control techniques, e.g. by using insecticide-treated uniforms.

Proguanil resistance in Plasmodium falciparum African isolates: assessment by mutation-specific polymerase chain reaction and in vitro susceptibility testing.

The antifolate proguanil is commonly used in the prophylaxis and treatment of Plasmodium falciparum malaria. A series of point mutations in the dihydrofolate reductase (DHFR) gene has been linked to differential susceptibility of varied P. falciparum clones or isolates to this drug. To survey the efficiency of proguanil prophylaxis in an African endemic region, and to evaluate the level of proguanil resistance in the corresponding parasite population, we performed drug susceptibility assays with P. falciparum isolates from Senegal, Kenya, and Niger. In parallel, we developed a mutation-specific polymerase chain reaction assay that enabled us to characterize mutations in the DHFR gene of the same isolates without in vitro parasite cultivation. We confirm previously available data showing that parasites harboring a point mutation from Ser108 to Asn present a decrease in susceptibility to cycloguanil (the active metabolite of proguanil), and we show that mutations in codons 51 and 59 appear to modulate the level of resistance to cycloguanil. No mutations in codons 16 and 164 were detected in resistant parasites, in contrast with results from some previous studies.

Caries prevalence in 12-year-old schoolchildren in New Caledonia.

This study reports on the most recent epidemiological survey undertaken in New Caledonia, a French dependency in the South Pacific. Three hundred and twenty-five 12-year-old children were selected from schools using the World Health Organization pathfinder sampling methodology. The results showed a DMFT of 4.09. This places New Caledonia in the 'moderate' category on the World Health Organization scale of caries severity for 12-year-old children. Two oral health risk groups were identified: Melanesian and Wallisian children. Different approaches to promoting oral health in New Caledonia, taking into account local socio-cultural traditions, are proposed.