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C Chemla

Publications and source records attributed to C Chemla.

At least 19 recordsLinked to original sources
PubMed2004

Population pharmacokinetics of pyrimethamine and sulfadoxine in children with congenital toxoplasmosis.

AIMS: To develop a population pharmacokinetic model for pyrimethamine (PYR) and sulfadoxine (SDX) in children with congenital toxoplasmosis. METHODS: Children were treated with PYR (1.25 mg kg(-1)) and SDX (25 mg kg(-1)) (Fansidar) plus folinic acid (Lederfoline) 5 mg). Plasma concentrations, available from a therapeutic drug monitoring database, were determined by high-performance liquid chromatography. Population pharmacokinetic analysis was performed using a nonlinear mixed effects model. RESULTS: Eighty-nine children, aged 1 week to 14 years and weighing 2.9-59 kg, were available for evaluation. Both PYR and SDX concentration-time profiles were best described by a one-compartment open model. Volume of plasma distribution (V) and clearance (CL) were significantly related to body weight (BW) using an allometric function. Typical CL and V estimates (95% confidence interval), for a child weighing 11 kg were 5.50 (5.28, 5.73) l day(-1) and 36 (33, 39) l for PYR and 0.26 (0.25, 0.27) l day(-1) and 2.1 (1.9, 2.3) l for SDX. For BW between 3.5 and 60 kg, plasma half-lives were predicted to vary from 4.0 to 5.2 days for PYR, and from 5.0 to 7.5 days for SDX. CONCLUSION: This study indicated that body weight influences PYR and SDX pharmacokinetics in children. To optimize PYR/SDX combination treatment in congenital toxoplasmosis, short dosing intervals in very young low-wight children are probably appropriate.

Adolescent↗
PubMed2003

Clinical value of specific immunoglobulin E detection by enzyme-linked immunosorbent assay in cases of acquired and congenital toxoplasmosis.

The clinical value of immunoenzymatic (enzyme-linked immunosorbent assay) detection of anti-Toxoplasma immunoglobulin E (IgE) was assessed by studying 2,036 sera from 792 subjects, comprising seronegative controls and subjects with acute, active, reactivated, or congenital toxoplasmosis. Included were nonimmunized adults; pregnant women with recently acquired infection (acute toxoplasmosis); immunocompetent subjects with recently acquired severe infection (active toxoplasmosis) expressed as fever, adenopathies, splenomegaly, pneumonia, meningitis, or disseminated infection; subjects-some of them immunocompromised-whose previously moderate IgG antibody levels rose, suggesting a reactivation of quiescent toxoplasmosis; and infants born to seroconverted mothers and evaluated for diagnosis of congenital infection and therapeutic management. Specific IgE antibodies were never detected in seronegative subjects. They were present in 85.7% of asymptomatic seroconverters and in 100% of seroconverters with overt toxoplasmosis, following two different kinetics: in the former, the specific IgE titer generally presented a brief peak 2 to 3 months postinfection and then fell rapidly, whereas specific IgE persisted at a very high titer for several months in the latter. IgE emerged concomitantly with the increase in IgG during toxoplasmic reactivation. For neonatal diagnosis of congenital toxoplasmosis, IgE was less informative than IgM and IgA (sensitivities, 59.5, 64.3, and 76.2%, respectively) and had a specificity of 91.9%. Nevertheless, simultaneous measurement of the three isotypes at birth improved the diagnostic yield to 81% relative to the combination of IgA and IgM. Emergence of specific IgE during postnatal treatment for congenital toxoplasmosis is a sign of poor adherence or inadequate dosing.

Acute Disease↗
PubMed2002

Preconception seroconversion and maternal seronegativity at delivery do not rule out the risk of congenital toxoplasmosis.

We describe two unusual cases of congenital toxoplasmosis, one occurring after preconception maternal infection with cervical adenopathies and the other occurring after maternal infection at the very end of pregnancy with maternal seronegativity at delivery. These documented cases of congenital toxoplasmosis demonstrate the value of extending the serologic monitoring period during pregnancy, according to the individual clinical context.

Adult↗
PubMed2001

Strategy for diagnosis of congenital toxoplasmosis: evaluation of methods comparing mothers and newborns and standard methods for postnatal detection of immunoglobulin G, M, and A antibodies.

In a study involving 14 laboratories supported by the European Community Biomed 2 program, we evaluated immunologic methods for the postnatal diagnosis of congenital toxoplasmosis (CT). Among babies born to mothers who seroconverted to positivity for toxoplasmosis during pregnancy, we analyzed 55 babies with CT on the basis of persistent anti-Toxoplasma immunoglobulin G (IgG) at 1 year of life and 50 control babies without anti-Toxoplasma IgG at 1 year of life in the absence of curative treatment with pyrimethamine-sulfonamides. We tested in-house methods such as the enzyme-linked immunofiltration assay (ELIFA) or Immunoblotting (IB) for the detection of IgG or IgM; these methods allowed comparison of the immunologic profiles of the mothers and the infants. We compared ELIFA and IB with a commercial enzyme immunoassay (EIA) or in-house immunosorbent agglutination assay (ISAGA) for the detection of IgM or IgA. The performances of combinations of methods were also assessed. A cumulative sensitivity of 98% during a 1-year follow-up was obtained with the ELIFA plus ISAGA combination. Only one case of CT was missed by the ELIFA plus ISAGA combination, whereas three cases were missed by the IB plus ISAGA combination, even though 48% of patients with CT were treated with pyrimethamine-sulfonamides, which are known to inhibit antibody neosynthesis. A similar performance was obtained with either ELIFA or IB in combination with EIA. The difference in performance between ELIFA plus ISAGA and IB plus ISAGA was not statistically significant (P = 0.31), and we conclude that both combinations of tests can be used for the diagnosis of CT in newborns.

Adult↗
PubMed1999

Detection of specific immunoglobulin E during maternal, fetal, and congenital toxoplasmosis.

Toxoplasma immunoglobulin E (IgE) antibodies in 664 serum samples were evaluated by using an immunocapture method with a suspension of tachyzoites prepared in the laboratory in order to evaluate its usefulness in the diagnosis of acute Toxoplasma gondii infection during pregnancy, congenital infection, and progressive toxoplasmosis. IgE antibodies were never detected in sera from seronegative women, from patients with chronic toxoplasma infection, or from infants without congenital toxoplasmosis. In contrast, they were detected in 86.6% of patients with toxoplasmic seroconversion, and compared with IgA and IgM, the short kinetics of IgE was useful to date the infection precisely. For the diagnosis of congenital toxoplasmosis, specific IgE detected was less frequently than IgM or IgA (25 versus 67.3%), but its detection during follow-up of children may be interesting, reflecting an immunological rebound. Finally, IgE was detected early and persisted longer in progressive toxoplasmosis with cervical adenopathies, so it was also a good marker of the evolution of toxoplasma infection.

Adolescent↗
PubMed1998

Pyrimethamine-sulfadoxine treatment of congenital toxoplasmosis: follow-up of 78 cases between 1980 and 1997. Reims Toxoplasmosis Group.

UNLABELLED: The purpose of this study was to determine the clinical and immunological outcome of 78 children with congenital toxoplasmosis treated with the pyrimethamine-sulfadoxine combination between 1980 and 1997. METHODS: Children were divided into 3 groups according to the initial duration of treatment (always including folinic acid, 5 mg/week by mouth), as follows: pyrimethamine (1.25 mg/kg every 15 d) + sulfadoxine (25 mg/kg every 15 d) for 12 months (Group 1, 47 children), or for 24 months, with or without prenatal therapy (respectively, Group 2, 19 children, and Group 3, 12 children). RESULTS: Chorioretinitis occurred in 23% of these 78 children. Four children had unilateral blindness, 1 had mild epileptic fits and 1 had psychomotor retardation. The lowest rate of sequelae were in Groups 2 and 3. Immunological rebounds, generally without clinical repercussions, occurred frequently (90% of cases on average) during, or more often after therapy, regardless of the treatment duration. Treatment was always well tolerated. CONCLUSIONS: Our current treatment strategy for congenital toxoplasmosis consists of a 24-month course of pyrimethamine-sulfadoxine (Fansidar) combined with folinic acid (Lederfoline). If the prenatal diagnosis is positive, we also prescribe this treatment to the mother until delivery. This combination offers satisfactory compliance, adequate serum concentrations, and good preventive efficacy.

Adolescent↗
PubMed1998

Prenatal diagnosis of congenital toxoplasmosis transmitted by an immunocompetent woman infected before conception. Reims Toxoplasmosis Group.

We report a rare case of congenital toxoplasmosis transmitted by an immunocompetent woman infected before conception. Active toxoplasmosis was suspected due to persistent lymphadenitis with specific IgM, IgA, IgE antibodies. Prenatal diagnosis based on amniocentesis and fetal blood sampling at 24 weeks' amenorrhoea was positive on amniotic fluid, and fetal infection was confirmed after termination. In our opinion such cases need the same monitoring as when seroconversion occurs during the first trimester. A pregnancy-free interval of six to nine months is recommended after proven patent toxoplasmosis seroconversion.

Adult↗
PubMed1997

[Screening for congenital toxoplasmosis: pregnancy outcome after prenatal diagnosis in 211 cases].

OBJECTIVE: To emphasize the importance of follow-up after birth of infants with an antenatal diagnosis of congenital toxoplasmosis. METHODS: Retrospective study from July 1987 through January 31 1995 on 211 women (214 fetuses) who had undergone ovular biopsy for toxoplasmosis seroconversion during pregnancy. RESULTS: Antenatal diagnosis was positive in 13 patients (6.2%). Four pregnancies were terminated during the second trimester. Delivery was triggered at 37 weeks gestation in one woman and in 8 others pregnancy was continued with Fansidar. All infants were born live with infraclinic disease. Two fetal deaths related to biopsy technique occurred (0.95%) and one pregnancy was terminated before the results had been obtained. Only 21.3% of the patients were delivered in our unit. A total of 197 infants were delivered with a negative antenatal diagnosis: 93 were healthy, 5 had congenital toxoplasmosis, 1 died at 3 months and 98 had no or incomplete follow-up. CONCLUSION: Incomplete post-natal follow-up is in contradiction with the excellent performance of antenatal diagnosis of congenital toxoplasmosis. Greater care is needed, especially since now only an amniocentisis is required to detect the parasite genome with polymerase chain reaction.

Adolescent↗
PubMed1997

A knowledge base for D. melanogaster gene interactions involved in pattern formation.

The understanding of pattern formation in Drosophila requires the handling of the many genetic and molecular interactions which occur between developmental genes. For that purpose, a knowledge base (KNIFE) has been developed in order to structure and manipulate the interaction data. KNIFE contains data about interactions published in the literature and gathered from various databases. These data are structured in an object knowledge representation system into various interrelated entities. KNIFE can be browsed through a WWW interface in order to select, classify and examine the objects and their references in other bases. It also provides specialised biological tools such as interaction network manipulation and diagnosis of missing interactions.

Animals↗
PubMed1996

Early neonatal diagnosis of congenital toxoplasmosis: value of comparative enzyme-linked immunofiltration assay immunological profiles and anti-Toxoplasma gondii immunoglobulin M (IgM) or IgA immunocapture and implications for postnatal therapeutic strategies.

Diagnostic strategies for congenital toxoplasmosis have changed profoundly in recent years. Immunological diagnostic methods, long considered disappointing, can now be used at a very early stage. Over a 3-year period, 1,050 infants at risk of congenital toxoplasmosis (born to 1,048 mothers infected during pregnancy) were monitored for a minimum of 12 months and a maximum of 7 years. More than 6,000 serum specimens were analyzed by comparative mother-infant immunological profiles (CIPs) based on an enzyme-linked immunofiltration assay (ELIFA) and an immunocapture method for the detection of specific immunoglobulin M (IgM) and IgA. IgG antibodies were also titrated. One hundred three cases of congenital toxoplasmosis were demonstrated. The CIP-ELIFA method had a better diagnostic yield (sensitivity, 90%) than specific IgM and/or IgA detection by immunocapture assay (sensitivity, 77%). By using a combination of these tests, congenital infection was diagnosed in the first month and the first 3 months of life in 90 and 94% of infants with toxoplasmosis, respectively, with a specificity of 99.8% and a positive predictive value of 99% at 8 months of age. This dual diagnostic approach (ELIFA and IgM-IgA immunocapture) is highly efficient and has important implications for therapy. Indeed, early postnatal diagnosis based on objective evidence enables therapy with pyrimethamine-sulfadoxine to be started immediately for 24 months, while spiramycin (which used to be given preventively for 9 to 12 months to all infants at risk) can be stopped after the first 3 months of life.

Animals↗
PubMed1995

[Ultrasonic signs of fetal toxoplasmosis. Review of the literature].

OBJECTIVE: Evaluate the frequency and discuss the mechanisms and the prognostic value of sonographic anomalies observed during the surveillance of seroconversion for toxoplasmosis during pregnancy. METHODS: Cases of seroconversion during pregnancy were collected from 6 teams working with similar protocols. There were 2,168 seroconversions. We focused on ultrasound anomalies reported. RESULTS: Ultrasound anomalies were reported in 48 cases including the 168 fetuses with proven contamination (fetal blood or amniotic fluid sample), i.e. 2.2% (48 cases out of 2,168) of the seroconversions and 28% (48 cases out of 168) of the contaminated fetuses. There were multiple lesions in 44% of the cases. Brain calcifications had been found in utero in 44% of the newborns with such anomalies. No case of microcephalia was reported. Isolated hepatomegalia (4 cases) was not an indication for medical abortion. Isolated ascitis can regress after antiparasite treatment (2 cases). Medical abortions were performed in 51% of the cases (34 cases out of 66) on the basis of ultrasound findings. CONCLUSION: Ultrasound examination is reliable but can only detect late, constituted and often irreversible lesions. Nevertheless, this examination can help in deciding on medical abortion.

Abortion, Therapeutic↗
PubMed1991

[Giant subcutaneous emphysema, pneumothorax and pneumomediastinum occurring in a 4-month-old infant recovering from anesthesia following surgery of a cleft palate].

The authors mention the case of pneumomediastinum and major cervico-facial-thoracic subcutaneous emphysema in a 4 month baby recovering from early surgery for a cleft palate, caused by a barotrauma (positive, pressure ventilation). After an emergency draining of the two pneumothorax, the situation evolved quickly, favourably and with no after effects whatsoever. They insist on the necessity of a rapid diagnosis concerning this rare complication (which can quickly evolve dramatically) and on the importance of pediatric anesthesia facilities.

Anesthesia Recovery Period↗
PubMed1990

[Caudal block in the surgical repair of vesico-renal reflux].

One hundred and twenty children have benefited from surgical cure for vesico-renal reflux under loco-regional anesthesia per caudal way, with use of a mixed solution of Lidocaine 1%, Bupivacaine 0.5%, with Adrenaline, along with a complementary narcosis. During the per operative time: the subsequent analgesia and muscular relief have always been excellent and lasted long enough. The hemodynamic status always showed a perfect stability. As to the ventilation, no deleterious effect could be demonstrated. Per operative blooding is reduced and central temperature is more easily controlled. During the post-operative time: the caudal anesthesia has allowed to maintain an efficient analgesia during a mean period of 12 hours which has been considered as sufficient. All the children went quickly back to a normal digestive function. There was no complication relevant to this technique.

Anesthesia, Caudal↗
PubMedDate not supplied

Frequency of specific anti-Toxoplasma gondii IgM, IgA and IgE in colombian patients with acute and chronic ocular toxoplasmosis.

We studied the frequency of specific anti-Toxoplasma IgM, IgA and IgE antibodies in serum of 28 immunocompetent Colombian patients, selected by ophthalmologists and with lesions that were compatible with ocular toxoplasmosis. Patients were classified in three groups: (i) group 1 consisted of ten patients with a first episode; (ii) group 2, with seven patients with a recurrence and (iii) group 3, consisted of eleven patients with chronic chorioretinal lesion without uveitis. We found that 10/28 (35%) of Colombian patients with ocular toxoplasmosis possessed at least one serological marker for Toxoplasma infection different from IgG. In group 1 (first episode), we found simultaneous presence of specific IgM plus IgA plus IgE in 1/10 (10%). In group 2 (recurrences) in 1/7 (14%) we found IgM and IgA test positives and in 1/7 (14%) we found IgM and IgE tests positives. In group 3 (toxoplasmic chorioretinal scar) the IgA serological test was positive in 2/11 (18%). These results show that serum IgM or IgA or IgE can be present during recurrences.

Acute Disease↗