[On the association of dental, cervicofacial, cardiac and digital malformations].
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Biomedical subjects
Publications and source records attributed to P Nicolas.
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Since plasma exchange (PE) represents a major treatment for patients suffering from systemic diseases, its influence on the kinetics of three drugs was investigated: vidarabine, used in patients with polyarteritis nodosa associated with hepatitis B virus (eight subjects), and diclofenac and paracetamol for investigative purposes (five subjects). This study confirmed that vidarabine is so rapidly deaminated to form hypoxanthine arabinoside (Hx-Ara) that no detectable concentrations were measured. Hx-Ara levels were used to evaluate vidarabine kinetics; 19.5 +/- 14.6 mg of Hx-Ara were removed by one PE during the first week of treatment (15 mg kg-1 d-1, continuous infusion) and 7.8 +/- 10.2 mg were eliminated by one PE during the second week of treatment (7.5 mg kg-1 d-1, continuous infusion). Based on the vidarabine intake per hour and the resulting quantity of Hx-Ara removed per hour, PE recovery was quite important (ca. 30 per cent), during both the first and second weeks of continuous infusion. Data were subject to large interindividual variability. However, these results do not favor vidarabine dosage supplementation in this indication because the duration of PE is less than 8 per cent of a daily administration period. For paracetamol (1 g, single oral dose) and diclofenac (100 mg, single oral dose), the fractions of drug removed during PE effected within 2 h of drug intake, were respectively 5.0 +/- 3.1 per cent and 13.6 +/- 9.5 per cent, while plasmapheretic clearance reached, respectively, 13.0 +/- 10.7 per cent of the systemic clearance for paracetamol and 23.0 +/- 1.0 per cent for diclofenac.
Rat thyrotropin-releasing hormone prohormone (pro-TRH) is a protein containing five copies of TRH, separated by connecting peptides. We have recently developed radioimmunoassays to synthetic peptides corresponding to prepro-TRH(160-169) and prepro-TRH(178-199). In the present study we have used these assays to investigate the ontogenesis of pro-TRH-derived peptides in the rat pancreas. Reverse-phase HPLC analysis of pancreatic extracts from 2-day-old rats showed the presence of two major immunoreactive peptides exhibiting the same retention time as synthetic prepro-TRH(160-169) and prepro-TRH(178-199), respectively. The concentrations of TRH and pro-TRH cryptic peptides in the rat pancreas rose rapidly after birth, reached a maximum at day 2-4 and decreased gradually afterwards. Streptozotocin treatment of newborn rats induced a marked decrease of TRH (96%), prepro-TRH(160-169) (97%) and prepro-TRH(178-199) content (94%) in pancreatic extracts. These results indicate that the evolution of TRH and pro-TRH-derived peptides follows the same pattern during the postnatal period. Our results also suggest that beta-cells are the only source of pro-TRH-derived peptides in the rat pancreas.
Using antisera to two pro-thyrotropin-releasing hormone (pro-TRH)-derived cryptic peptides, we have studies by immunocytochemistry the ultrastructural localization of pro-TRH in the rat raphe nuclei. The same results were obtained with both antisera. Immunostaining was found in cell bodies, dendrites and endings. In cell bodies, the reaction product was restricted to Golgi saccules and dense core vesicles which were very few in number. In dendrites, the staining was rather diffuse without any association with specific organelles. These results suggest that the Golgi apparatus might be involved in pro-TRH processing.
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One hundred four serogroup A meningococci in our collection, isolated in Africa from 1988 to 1999, were characterized by multilocus sequence typing (MLST). Our results and data from the Internet indicate that sequence type 5 (ST-5) strains were responsible for most of African outbreaks and sporadic cases during this period. In 1995, a new clone, characterized by ST-7 sequence, emerged and was responsible for severe outbreaks in Chad (1998) and Sudan (1999). MLST and epidemiologic data indicate that ST-5 and ST-7 represent two virulent clones. These two STs, which belong to subgroup III, differ only in the pgm locus: allele pgm3 is characteristic for ST-5 and allele pgm19 for ST-7. Subgroup III strains were responsible for two pandemics in the 1960s and 1980s. Our data show that the third subgroup III pandemic has now reached Africa.
In North Cameroon, venom inoculations by Echis Carinatus are frequent and severe and thus pose a serious problem at Public Health Services. 48 bites without antivenomous serum injection have been considered in Garoua, Benoue valley North Cameroon. Without antivenomous serum light inoculations heal spontaneous by in a couple of days about 20% of the average clinical forms are evoluting insidiously to severe globulolysis. The great majority of severe inoculations lead to dreadful hemorrhagic threatening the life of patients. New borns and infants are particularly exposed, it is not advisable to inject systematically antivenomous serum. But it has to be considered as compulsory in the three following clinical situations before 11 years of age, venom inoculation often brings about fast aggravation, mainly in new borns, after 11 years and at adult age, when clinical signs are of great concern, when hemoglobinometry indicates less than 9 gr/100 ml after 48 hours of evolution in youngs and adults, but without any symptom of severity.
Eclampsia is a serious complication at the end of pregnancy. This retrospective study over a 5-year period at the Libreville CHU hospital shows that the incidence of 0.12 p. cent is comparable to the incidence fond in other countries at a similar level of development. Promoting causes include youth of the patients, twin births, the "cold" season, the lack of follow-up after prenatal consultations. The consequences are increased maternal and perinatal death. Cesarean section remains the best way of dealing with an attack of eclampsia and improves both maternal and fetal prognosis. It is possible to eliminate, or at least reduce, the number of cases by developing conscientious and regular prenatal consultations.
Plasma exchange has been proposed for treating diseases mediated by circulating immune complexes. Removal of drugs during plasma exchange is a complex function of pharmacokinetic characteristics and specifications of the plasma exchange procedure: the time of plasma exchange, the filtered volume of plasma, the number of procedure. The effect of plasma exchange on the kinetics of drugs can be evaluated by different parameters: amount eliminated, extracorporeal clearance, fractional drug removal, extracorporeal elimination rate constant. Knowledge of the impact of plasma on the elimination of drugs is essential to the design of the dosage regimen in patients treated with plasma exchange. The fraction of the estimated amount in body removed by plasma exchange is the best parameter to evaluate the effectiveness of the exchange procedure, but it is necessary to know the proportion of body pool of drug at the start of the plasma exchange. Drug recovery by each exchange may account for 0.5%-30% of the dose. Controlled studies are needed to quantify the effects of plasma exchange on drug therapy. Dosage adjustment is sometimes required.
New emerging atypical forms of malaria, characterized by weak parasitemia, among peoples without premunition, back from Plasmodium falciparum resistant areas, make it necessary to use rapid, sensitive, reliable methods of parasitologic diagnosis. This work concerned two different populations: 394 expatriates back from a 4 months stage in endemic areas. 12 patients admitted for suspected of proved malaria. Authors have studied, by double blind method, versus thin film, two fluorescent techniques: a direct immunofluorescence, the Monofluo kit Falciparum of Diagnostic Pasteur. A nucleic acid fluorescence, on blood samples centrifuged in capillary tubes, the Q.B.C. test of Becton-Dickinson. Both methods seem of great interest for epidemiological surveys. The Q.B.C. test has showed more sensitivity than the thin film: it's rapidity of realisation indicates it for urgent diagnosis.
Using our knowledge of recent discoveries on chronic HBV hepatitis, we consider the indispensable addition that the close study of HBV replication represents. An accurate evaluation of this replication can be obtained through quantitative research of the HBc antigen on liver. The detection is currently facilitated by the production and marketing of good quality antisera and revelation systems. The routine application of these techniques by classical histology departments is possible.
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The current knowledge on the biosynthetic mechanisms of three hypothalamic neuropeptides, neurophysins, vasopressin and somatostatin, is reviewed. Both neurophysin and vasopressin appear to be first synthesized as higher molecular weight precursors. The methodology elaborated allows to characterize essentially two main forms with apparent Mr similar to or approximately 25 000 and 80 000 respectively. It can be demonstrated that both neurophysin and vasopressin are derived from common precursors.
To declare bioequivalent two different formulations of one active drug, bioavailability studies are conducted, usually based on area under the plasma concentration-time curves and peak concentrations. The decision follows a statistical basis with right statement of the hypotheses of bioequivalence that are described. This procedure allows to control the consumer risk of falsely accepting bioequivalence while minimizing the new formulation risk of erroneously rejecting bioequivalence. Six decision rules meeting these criteria are reviewed and compared with numerical data: classic confidence interval; symmetric confidence interval; Hauck-Anderson method; two one-sided tests procedure; bayesian method; non parametric confidence interval. The six rules all have very similar performance. However, the bayesian procedure which gives a probability of the location of the true relative bioavailability could likely complete the two one-sided tests procedure and/or the classic confidence interval method that are recommended in regulatory guidelines. Some other statistical points that have received different interpretation in the international regulations are finally evoked and discussed.