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Biomedical subjects

S Lafon

Publications and source records attributed to S Lafon.

12 recordsLinked to original sources
PubMed2005

Geometric diffusions as a tool for harmonic analysis and structure definition of data: diffusion maps.

We provide a framework for structural multiscale geometric organization of graphs and subsets of R(n). We use diffusion semigroups to generate multiscale geometries in order to organize and represent complex structures. We show that appropriately selected eigenfunctions or scaling functions of Markov matrices, which describe local transitions, lead to macroscopic descriptions at different scales. The process of iterating or diffusing the Markov matrix is seen as a generalization of some aspects of the Newtonian paradigm, in which local infinitesimal transitions of a system lead to global macroscopic descriptions by integration. We provide a unified view of ideas from data analysis, machine learning, and numerical analysis.

Journal Article↗
PubMed2005

Geometric diffusions as a tool for harmonic analysis and structure definition of data: multiscale methods.

In the companion article, a framework for structural multiscale geometric organization of subsets of R(n) and of graphs was introduced. Here, diffusion semigroups are used to generate multiscale analyses in order to organize and represent complex structures. We emphasize the multiscale nature of these problems and build scaling functions of Markov matrices (describing local transitions) that lead to macroscopic descriptions at different scales. The process of iterating or diffusing the Markov matrix is seen as a generalization of some aspects of the Newtonian paradigm, in which local infinitesimal transitions of a system lead to global macroscopic descriptions by integration. This article deals with the construction of fast-order N algorithms for data representation and for homogenization of heterogeneous structures.

Journal Article↗
PubMed2001

Hypersensitivity reactions during therapy with the nucleoside reverse transcriptase inhibitor abacavir.

BACKGROUND: Hypersensitivity reactions consist of a variable group of clinical findings and have been described for a wide variety of chemical compounds. OBJECTIVE: This review characterizes the clinical profile of hypersensitivity to the nucleoside reverse transcriptase inhibitor abacavir sulfate. METHODS: We performed a retrospective medical review of pooled adverse events data from approximately 200,000 patients who received abacavir in clinical trials, through expanded-access programs, or by prescription from 1996 through 2000. Screened cases of hypersensitivity were classified as either definitive or probable. Definitive cases were identified when initial symptoms resolved on interruption of abacavir therapy and returned on reintroduction of abacavir therapy. RESULTS: A total of 1803 cases were identified, 1302 in the 30,595 patients participating in clinical trials or the expanded-access program and 501 in patients from the post-marketing experience. On review, 176 (9.8%) of these cases were considered definitive and the remainder probable. Based on the 1302 cases identified in clinical trials or the expanded-access program, the calculated incidence of hypersensitivity was 4.3%. Symptoms reported in > or = 20% of cases of this multiorgan reaction included fever, rash, malaise/fatigue, and gastrointestinal symptoms such as nausea, vomiting, and diarrhea, among others. Respiratory symptoms occurred in 30% of cases and included dyspnea (12%), cough (10%), and pharyngitis (6%). In 90% of cases, hypersensitivity reactions occurred within the first 6 weeks after initiation of abacavir (median time, 11 days); after an initial reaction, rechallenge with abacavir resulted in the reappearance of symptoms within hours of reexposure. Hypotension was present in 25% of these rechallenge reactions. Among patients who received abacavir in clinical trials, the mortality rate was 0.03% (3 per 10,000 patients). CONCLUSIONS: Hypersensitivity to abacavir is an idiosyncratic reaction and a distinct clinical syndrome characterized predominantly by systemic involvement. It can be expected to appear as a treatment-limiting event in approximately 5% of patients. The appearance of clinical symptoms consistent with this syndrome mandates immediate discontinuation of abacavir. Hypersensitivity to abacavir is an absolute contraindication to subsequent treatment with any formulation that includes this agent.

Clinical Trials, Phase II as Topic↗
PubMed1997

A simple Trypanosoma cruzi enzyme-linked immunoassay for control of human infection in nonendemic areas.

An enzyme linked immunosorbent assay (ELISA) was developed for detecting IgM and IgG antibodies against Trypanosoma cruzi in blood bank donors from endemic or nonendemic areas. A crude extract of trypomastigotes from cultures was used as antigen. A total of 494 serum samples from patients with acute, congenital, or chronic form of Chagas' disease, and from healthy French individuals were studied. The sensitivity of the ELISA was determined with 89 serum samples from chagasic patients and was evaluated to 98.8%. The specificity was determined with 405 serum samples from French blood transfusion centers donors and evaluated to 98.3%. Two hundred and eighty-five serum samples from blood donors from Argentina and Brazil were also tested. Furthermore, in order to assess the absence of cross-reactivity with other protozoan infections, we studied 86 serum samples including (i) 32 individuals with cutaneous leishmaniasis living in a T. cruzi endemic region of Bolivia, and (ii) 54 patients from nonendemic area for Chagas' disease, 19 of them with kala-azar and 35 others with malaria.

Animals↗
PubMed1995

Prevalence of anti-R-13 antibodies in human Trypanosoma cruzi infection.

Infection with Trypanosoma cruzi develops in three phases: acute, indeterminate or asymptomatic, and chronic phase (with cardiac or digestive manifestations). Moreover, transmission may occur from infected mothers to newborn, the so-called congenital form. In the present study, humoral responses against T. cruzi total extract and against the 13 amino acid peptide named R-13 derived from the parasite ribosomal P protein, previously described as a possible marker of chronic Chagas heart disease, were determined in chagasic patients and in blood bank donors from endemic areas. While in sera from acute phase, only IgM anti-T.cruzi response was observed, both IgM and IgG anti-T. cruzi antibodies were detected in sera from congenitally infected newborns. The percentage of positive response in sera from blood bank donors was relatively high in endemic regions. Antibodies against the R-13 peptide were present in a large proportion of cardiac chagasic patients but were totally lacking in patients with digestive form of Chagas' disease. Furthermore, anti-R-13 positive responses were detected in congenitally infected newborns.

Acute Disease↗
PubMed1993

The chronic presence of the parasite, and anti-P autoimmunity in Chagas disease: the Trypanosoma cruzi ribosomal P proteins, and their recognition by the host immune system.

Molecular expression cloning techniques revealed that patients with the severest clinical form of Chagas disease, chronic Chagas heart disease, presented a strong humoral response against the cloned C-terminal portion of a Trypanosoma cruzi ribosomal P protein. Parasite P antigens identification led to characterize the ribosomal P protein system in T. cruzi. Their exposed location on the ribosome, and the "amplification" of their parasite specific, serine free C-terminal domain, generate a strong parasite specific anti-P response, that in certain cases may induce anti-P autoimmunity.

Amino Acid Sequence↗
PubMed1992

The 70-kDa heat-shock protein is a major antigenic determinant in human Trypanosoma cruzi/Leishmania braziliensis braziliensis mixed infection.

Five sera from Bolivian individuals chronically infected by Trypanosoma cruzi, and suffering an active Leishmania braziliensis braziliensis metastatic mucocutaneous lesion were characterized. They reacted with the T. cruzi recombinant antigens that are currently used as Chagas diagnostic reagents, and with several L. b. braziliensis proteins as assessed by Western blot. These sera showed an intense reaction with a T. cruzi and an L. b. braziliensis polypeptide of about 70 kDa. Expression cloning techniques demonstrated that the target of this immunologic reaction was a cross-reactive antigen, the 70-kDa heat-shock protein (HSP 70). High levels of anti-HSP 70 reactivity and positive reactions with all or some of the T. cruzi recombinant antigens JL7, JL8, and JL5, defined a serologic pattern that was characteristic of the T. cruzi/L. b. braziliensis mixed infection.

Amino Acid Sequence↗
PubMed1991

Recombinant Trypanosoma cruzi antigens and Chagas' disease diagnosis: analysis of a workshop.

A workshop organized by the Ibero-American Project of Biotechnology evaluated the diagnostic potential of several cloned Trypanosoma cruzi recombinant antigens for Chagas' disease serodiagnosis. A set of recombinants, Antigen 2, Antigen 13, SAPA, H49, A13, JL5, JL7, JL8, JL9, and RA1 provided by three different South American laboratories were probed with a panel of 236 South American serum samples. Antigens JL7, H49, Antigen 2, and A13 scored as the best diagnostic recombinant reagents. The results suggested that the main advantage of using cloned peptides for chronic Chagas' disease diagnosis resided in their highly specific immunoreactive properties.

Animals↗