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Biomedical subjects

M Marchand

Publications and source records attributed to M Marchand.

At least 19 recordsLinked to original sources
PubMed2000

'Stealth' corona-core nanoparticles surface modified by polyethylene glycol (PEG): influences of the corona (PEG chain length and surface density) and of the core composition on phagocytic uptake and plasma protein adsorption.

Nanoparticles possessing poly(ethylene glycol) (PEG) chains on their surface have been described as blood persistent drug delivery system with potential applications for intravenous drug administration. Considering the importance of protein interactions with injected colloidal dug carriers with regard to their in vivo fate, we analysed plasma protein adsorption onto biodegradable PEG-coated poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA) and poly(varepsilon-caprolactone) (PCL) nanoparticles employing two-dimensional gel electrophoresis (2-D PAGE). A series of corona/core nanoparticles of sizes 160-270 nm were prepared from diblock PEG-PLA, PEG-PLGA and PEG-PCL and from PEG-PLA:PLA blends. The PEG Mw was varied from 2000-20000 g/mole and the particles were prepared using different PEG contents. It was thus possible to study the influence of the PEG corona thickness and density, as well as the influence of the nature of the core (PLA, PLGA or PCL), on the competitive plasma protein adsorption, zeta potential and particle uptake by polymorphonuclear (PMN) cells. 2-D PAGE studies showed that plasma protein adsorption on PEG-coated PLA nanospheres strongly depends on the PEG molecular weight (Mw) (i.e. PEG chain length at the particle surface) as well as on the PEG content in the particles (i.e. PEG chain density at the surface of the particles). Whatever the thickness or the density of the corona, the qualitative composition of the plasma protein adsorption patterns was very similar, showing that adsorption was governed by interaction with a PLA surface protected more or less by PEG chains. The main spots on the gels were albumin, fibrinogen, IgG, Ig light chains, and the apolipoproteins apoA-I and apoE. For particles made of PEG-PLA45K with different PEG Mw, a maximal reduction in protein adsorption was found for a PEG Mw of 5000 g/mole. For nanospheres differing in their PEG content from 0.5 to 20 wt %, a PEG content between 2 and 5 wt % was determined as a threshold value for optimal protein resistance. When increasing the PEG content in the nanoparticles above 5 wt % no further reduction in protein adsorption was achieved. Phagocytosis by PMN studied using chemiluminescence and zeta potential data agreed well with these findings: the same PEG surface density threshold was found to ensure simultaneously efficient steric stabilization and to avoid the uptake by PMN cells. Supposing all the PEG chains migrate to the surface, this would correspond to a distance of about 1.5 nm between two terminally attached PEG chains in the covering 'brush'. Particles from PEG5K-PLA45K, PEG5K-PLGA45K and PEG5K-PCL45K copolymers enabled to study the influence of the core on plasma protein adsorption, all other parameters (corona thickness and density) being kept constant. Adsorption patterns were in good qualitative agreement with each other. Only a few protein species were exclusively present just on one type of nanoparticle. However, the extent of proteins adsorbed differed in a large extent from one particle to another. In vivo studies could help elucidating the role of the type and amount of proteins adsorbed on the fate of the nanoparticles after intraveinous administration, as a function of the nature of their core. These results could be useful in the design of long circulating intravenously injectable biodegradable drug carriers endowed with protein resistant properties and low phagocytic uptake.

Journal Article↗
PubMed2000

Partial deletion of the AGXT gene (EX1_EX7del): A new genotype in hyperoxaluria type 1.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal (2q37.3) recessive metabolic disease caused by a deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate amino transferase. Molecular heterogeneity is important in PH1 as most of the patients (if the parents are unrelated) are compound heterozygotes for rare mutations. We describe the first large deletion in the AGXT gene, removing exons 1 to 7 (EX1_EX7del) that was responsible for one case of severe PH1. This 10 kb deletion was identified by Southern blotting of genomic DNA digested by Xba I and hybridized with different exonic probes. Both parents (from Turkey) are first cousin and carry the deletion. It is of note that the presently reported patient did not exhibit any AGT catalytic activity and even so, he progressed towards end-stage renal disease only at 19 years old.

Adult↗
PubMed2000

Cerebrospinal fluid protein concentrations in children: age-related values in patients without disorders of the central nervous system.

BACKGROUND: The published reference values for cerebrospinal fluid (CSF) total protein concentrations in children suffer from two major drawbacks: (a) the age-related range often is too broad when applied to the steeply falling concentrations in early infancy; and (b) no values have been published for widely used dry chemistry methods. METHODS: We conducted a 2-year retrospective survey of CSF results obtained in a children's hospital with a dry chemistry-based method set up on the Vitros 700 analyzer. RESULTS: The data related to ambulatory children up to 16 years of age and term neonates with no clinical or biological signs of brain disease (n = 1074). Seven age groups with significantly different CSF protein values were identified, and their age-related percentiles (5th, 50th, and 95th) were determined. On the basis of the upper 95th percentile, from age 0 to 6 months the CSF protein concentrations fell rapidly from 1.08 to 0.40 g/L. A plateau (0.32 g/L) was reached from age 6 months to 10 years, followed by a slight increase (0.41 g/L) in the 10-16 years age range. CONCLUSIONS: These results imply that CSF total protein concentrations in the pediatric setting, particularly in infants, must always be interpreted with regard to narrow age-related reference values to avoid false-positive results.

Adolescent↗
PubMed1999

Antibodies to platelet factor 4-heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low-molecular-weight heparin : clinical implications for heparin-induced thrombocytopenia.

BACKGROUND: Cardiopulmonary bypass (CPB) induces platelet activation with release of platelet factor 4 (PF4), and patients are exposed to high doses of heparin (H). We investigated whether this contributes to the development of antibodies to H-PF4 and heparin-induced thrombocytopenia (HIT). METHODS AND RESULTS: CPB was performed with unfractionated heparin (UFH) in 328 patients. After surgery, patients received UFH (calcium heparin, 200 IU. kg-1. d-1) (group 1, n=157) or low-molecular-weight heparin (LMWH, Dalteparin, 5000 IU once daily) (group 2, n=171). Eight days after surgery, antibodies to H-PF4 were present in 83 patients (25.3%), 46 in group 1 and 37 in group 2 (P=0.12). Most patients (61%) had IgG1 to H-PF4, but only 8 samples with antibodies induced platelet activation with positive results on serotonin release assay. HIT occurred in 6 patients in group 1, but no thrombocytopenia was observed in subjects receiving LMWH, although 2 had high levels of antibodies with positive serotonin release assay results. When antibodies to H-PF4 were present, mean platelet counts were lower only in patients with FcgammaRIIA R/R131 platelets. CONCLUSIONS: These results provide evidence that the development of antibodies to H-PF4 after CPB performed with UFH is not influenced by the postoperative heparin treatment. The antibodies associated with high risk of HIT are mainly IgG1, which is present at high titers in the plasma of patients continuously treated with UFH.

Adolescent↗
PubMed1999

Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1.

Thirty-nine tumor-bearing patients with metastatic melanoma were treated with 3 subcutaneous injections of the MAGE-3.A1 peptide at monthly intervals. No significant toxicity was observed. Of the 25 patients who received the complete treatment, 7 displayed significant tumor regressions. All but one of these regressions involved cutaneous metastases. Three regressions were complete and 2 of these led to a disease-free state, which persisted for more than 2 years after the beginning of treatment. No evidence for a cytolytic T lymphocyte (CTL) response was found in the blood of the 4 patients who were analyzed, including 2 who displayed complete tumor regression. Our results suggest that injection of the MAGE-3.A1 peptide induced tumor regression in a significant number of the patients, even though no massive CTL response was produced.

Adult↗
PubMed1999

Detection of fluoxetine in brain, blood, liver and hair of rats using gas chromatography-mass spectrometry.

This study reports the measurements of fluoxetine in discrete brain regions, blood, liver and hair of male rats injected with 10 mg/kg fluoxetine HCl for 15 consecutive days. Concentrations of the antidepressant were obtained by gas chromatography-mass spectrometry (GC-MS) methodology. In brain, fluoxetine levels were unevenly distributed, with the raphé nucleus containing the highest amounts relative to the hypothalamus or striatum. Fluoxetine was also measured in blood and liver roughly paralleling those ratios described in previous rodent studies. Of potential interest, fluoxetine was found to accumulate in rat hair after chronic treatment. Detection of fluoxetine in hair by GC-MS could be used as a marker for probative analyses.

Animals↗
PubMed1999

Derivation of tumor-specific cytolytic T-cell clones from two lung cancer patients with long survival.

We derived lung carcinoma cell lines from tumor material resected from a patient with small-cell lung cancer (SCLC) and from a patient with non-small-cell lung cancer (NSCLC). The patient with NSCLC was vaccinated with irradiated autologous tumor cells. The two patients enjoyed an exceptionally favorable clinical evolution and are currently without signs of cancer 10 and 8 yr after their diagnoses, respectively. Autologous mixed lymphocyte-tumor cell cultures (MLTC) were produced with blood lymphocytes stimulated with irradiated autologous tumor cells. The first patient's SCLC cells, which carried a small amount of human leukocyte antigen (HLA) class I molecules, were incubated with interferon-gamma (IFN-gamma) before being used as stimulator cells. A cytolytic T-lymphocyte (CTL) clone was derived that specifically lysed the IFN-gamma-treated SCLC cells but did not lyse untreated tumor cells or autologous lymphoblasts. Clones of autologous tumor-specific CTL, directed against the NSCLC cells of the other patient, were also obtained. These tumor cells carried a higher level of HLA class I molecules and were lysed by the CTL without incubation with IFN-gamma. Altogether, these results indicate that SCLC and NSCLC cancer cells can be recognized by autologous CTL, and might therefore be susceptible to specific immunotherapy.

Carcinoma, Non-Small-Cell Lung↗
PubMed1999

[Immediate and mid-term results of surgery for aortic coarctation in children under 6 months of age].

The aim of this study was to assess the impact of medical and surgical advances on the results of surgery of coarctation of the aorta without major associated cardiac malformations in children aged under 6 months, operated by the surgical team of Tours over a period of 17 years. A retrospective analysis of patients' files allowed inclusion of 75 children: 34 in group I (1980-1988) and 41 in group II (1989-1996). The age at diagnosis, mode of presentation, clinical and echocardiographic parameters, initially and at surgery, were comparable in the two groups. In group II, the surgical procedure of choice changed to the Crafoord procedure (p = 0.0001), the peroperative haemodynamic complications were less common (p = 0.04), patients were operated sooner after diagnosis (p = 0.002) with a higher number of neonates (p = 0.04). There were two early deaths in group I and two late deaths in group II. Six children (8.2%) had recurrence of coarctation. This was more common in children operated before 1 month of age (p = 0.0001) and in cases of hypoplasia of the aortic arch (p < 0.01). The risk of recoarctation in neonates was lower in group II than in group I (p < 0.02). At medium term, the coarctation was considered well repaired in 93.7% and 92.6% of patients in group I and II respectively. However, hypertension on exercise was observed in 8 of the 19 children studied. Finally, secondary surgical or instrumental procedures were required in 9 children to treat associated cardiovascular abnormalities. The authors conclude that in recent years, aortic coarctation was repaired earlier, mainly by a modified Crafoord procedure, with fewer haemodynamic complications, without early mortality. The risk of recoarctation remains low but persistent in neonates. At medium term, hypertension on exercise is a common problem even in children with excellent repairs.

Age Factors↗
PubMed1998

T-DNA mediated disruption of essential gametophytic genes in Arabidopsis is unexpectedly rare and cannot be inferred from segregation distortion alone.

Many genes are thought to be expressed during the haploid phase in plants, however, very few haploid-specific genes have been isolated so far. T-DNA insertion mutagenesis is a powerful tool for generating mutations that affect gametophyte viability and function, as disruption of a gene essential for these processes should lead to a defect in the transmission of the gametes. Mutants can therefore be screened on the basis of segregation distortion for a reporter resistance gene contained in the T-DNA. We have screened the Versailles collection of Arabidopsis transformants for 1:1 KanR:KanS segregation after selfing, focussing on gametophyte mutations which show normal transmission through one gametophyte and cause lethality or dysfunction of the other. Only 1.3% (207) of the 16,000 lines screened were scored as good candidates. Thorough genetic analysis of 38 putative T-DNA transmission defect lines (Ttd) identified 8 defective gametophyte mutants, which all showed 0 to 1% T-DNA transmission through the pollen. During the screen, we observed a high background of low-penetrance mutations, often affecting the function of both gametophytes, and many lines which were likely to carry chromosomal rearrangements. The reasons for the small number of retained lines (all male gametophytic) are discussed, as well as the finding that, for most of them, residual T-DNA transmission is obtained through the affected gametophyte.

Arabidopsis↗
PubMed1998

Mutations of the beta2-microglobulin gene result in a lack of HLA class I molecules on melanoma cells of two patients immunized with MAGE peptides.

Mutations have been identified in the beta2-microglobulin gene of tumor cells of two metastatic melanoma patients who received immunizations with MAGE peptides. One mutation abolishes the start codon whereas the other introduces a premature stop codon. The second beta2-microglobulin allele of both tumors appears to be lost on the basis of sequence data and loss of microsatellite heterozygosity. The lack of beta2-microglobulin gene product results in the absence of HLA class I antigens on the surface of the tumor cells. This may explain why the tumors of both patients progressed despite the immunization treatment and shows the necessity of analyzing in depth the antigen presentation capability of the tumor cells for the interpretation of clinical trials involving anti-tumor vaccination.

Antigens, Neoplasm↗
PubMed1998

Twelve-year experience with Carpentier-Edwards PERIMOUNT pericardial valve in the mitral position: a multicenter study.

BACKGROUND AND AIMS OF THE STUDY: The study aim was to assess the durability of the Carpentier-Edwards PERIMOUNT pericardial bioprosthesis in the mitral position. METHODS: This seven-center retrospective clinical study involved the follow up of 333 patients who underwent isolated mitral valve replacement and 102 patients who underwent double (mitral and aortic) valve replacement with the PERIMOUNT pericardial valve between 1984 and 1989. Mean patient age at implant was 60.7 +/- 11.6 years; 41.1% were males. The most common etiology was rheumatic heart disease (53.9%) and the most common mechanism mitral insufficiency. All patients but six were followed for an average of 7.2 +/- 3.6 years after surgery; total follow up was 3071.7 patient-years (pt-yr). RESULTS: The total operative mortality rate was 7.6%; this included a valve-related mortality rate of 0.2%. The late mortality rate was 5.2% per pt-yr, of which 1.4% per pt-yr was considered valve-related. At 11 years, the overall actuarial survival rate was 53.3 +/- 2.8%, and actuarial freedom from valve-related death 83.9 +/- 2.6%. At follow up, 80% of patients were in NYHA class I or II, and 74% showed improvement. Twenty-eight incidences of deterioration requiring explant were observed. At 11 years the actuarial freedom from explant due to structural failure was 84.9 +/- 3.1%. Rates of structural failure decreased with age: the actuarial freedom from explant due to structural failure was 78.1 +/- 4.8% for patients aged < or = 60 years, 89.4 +/- 4.4% for those aged 61-70 years, and 100% for those aged over 71 years. CONCLUSION: The Carpentier-Edwards PERIMOUNT pericardial bioprosthesis is a reliable choice when a tissue valve is required, especially in patients over 60 years of age.

Bioprosthesis↗
PubMed1998

[Clinical, hemodynamic and angiographic results of total cavo-pulmonary connection].

The aim of the study was to assess the short and medium term results of total cavo-pulmonary connection based on analysis of the functional status, the cavo-pulmonary circulation and the surgical techniques, and the hepatic consequences. Fifteen patients with congenital defects beyond repair were treated by total cavo-pulmonary connection at Tours between March 1st 1992 and July 30th 1996. There were 12 children (mean age: 6.3 years) and 3 adults aged 25 to 28. Results were assessed by clinical examination, hepatic function tests and cardiovascular investigations including right heart catheterisation with angiography in 14 patients. There were no fatalities. Seven patients were in functional Class I and 8 in Class II at medium term (average follow-up of 33 months). Hepatic function was mildly abnormal in all patients with an increase in serum bilirubin and gamma GT, and a decrease in the coagulation factors. The mean pressures in the atrial channel were 12 mmHg (9-16 mmHg), in the superior vena 13.2 mmHg (10-18 mmHg), in the right pulmonary artery 9.5 mmHg (7-15 mmHg) and 11.6 mmHg (8-16 mmHg) in the left pulmonary artery. Significant residual stenosis of a pulmonary branch was observed in 2 cases. The cavo-pulmonary anastomoses were out of line, one from the other, in all cases. The atrial channel was tubular in 9 cases and dilated with slight stagnation of the contrast medium in its inferior region in 5 cases. Total cavo-pulmonary connection transformed the clinical status of these patients but was associated with minor abnormalities of liver function. The quality of the cavo-pulmonary circulation and the surgical anastomoses was estimated to be satisfactory in the majority of cases.

Adult↗
PubMed1997

A preliminary evaluation of a recombinant circumsporozoite protein vaccine against Plasmodium falciparum malaria. RTS,S Malaria Vaccine Evaluation Group.

BACKGROUND: The candidate vaccines against malaria are poorly immunogenic and thus have been ineffective in preventing infection. We developed a vaccine based on the circumsporozoite protein of Plasmodium falciparum that incorporates adjuvants selected to enhance the immune response. METHODS: The antigen consists of a hybrid in which the circumsporozoite protein fused to hepatitis B surface antigen (HBsAg) is expressed together with unfused HBsAg. We evaluated three formulations of this antigen in an unblinded trial in 46 subjects who had never been exposed to malaria. RESULTS: Two of the vaccine formulations were highly immunogenic. Four subjects had adverse systemic reactions that may have resulted from the intensity of the immune response after the second dose, which led us to reduce the third dose. Twenty-two vaccinated subjects and six unimmunized controls underwent a challenge consisting of bites from mosquitoes infected with P. falciparum. Malaria developed in all six control subjects, seven of eight subjects who received vaccine 1, and five of seven subjects who received vaccine 2. In contrast, only one of seven subjects who received vaccine 3 became infected (relative risk of infection, 0.14; 95 percent confidence interval, 0.02 to 0.88; P<0.005). CONCLUSIONS: A recombinant vaccine based on fusion of the circumsporozoite protein and HBsAg plus a potent adjuvant can protect against experimental challenge with P. falciparum sporozoites. After additional studies of protective immunity and the vaccination schedule, field trials are indicated for this new vaccine against P. falciparum malaria.

Adjuvants, Immunologic↗
PubMed1997

The single-breath nitrogen test in coal miners: factors associated with failure to perform.

The single-breath nitrogen washout (SBN2) test was used, along with spirometry, in the baseline examination of a longitudinal study in a cohort of active coal miners from North-eastern France. The procedure was computerized, allowing the technician to coach and encourage the subject, and excluding computation errors. While all miners performed satisfactory spirometry, a significant number were unable to meet the National Heart and Lung Institute recommendation concerning a 10% agreement of vital capacities. When the limits were set at +/-12%, 57 miners (24.2%) were still classified as failing to perform. When compared to those who succeeded, those failing proved to be significantly older, had more cumulated dust exposure, a higher prevalence of chronic cough and sputum, and a trend for more micronodulation on the chest radiographs. The ventilatory function did not differ between the two groups. These results confirm previous data on spirometric test failure concerning older age and respiratory symptoms, extending them to the SBN2 test. The present study further indicates that dust exposure and roentgenologic pneumoconiosis nodulation are associated with failure to perform the SBN2 test.

Adult↗
PubMed1997

Influence of age on valve related events with Carpentier-Edwards pericardial bioprosthesis.

UNLABELLED: Age is the most important factor for the durability of biological valves. With an original design the Carpentier-Edwards pericardial valve showed improved results at 10 years. The influence of age on valve related complications is studied with a 10 year follow up on 807 valvular replacements. METHODS: Between January 1984 and December 1993, 807 patients underwent valve replacements with a Carpentier-Edwards pericardial bioprosthesis. Patients, 193 were younger than 60 years, 284 between 60 and 70 years and 330 patients were older than 70 years. All patients but seven were followed up for an average of 4.18 years after their operation and total follow up was 3373 patient years. Patients were divided into three groups of age: group I, less than 60 years; group II, 60-70 years; group III, over 70 years. A retrospective comparison was made between age groups. RESULTS: At 11 years, valve related complications included 97 patients with 27 valve related deaths. Rates of valve related death increase with age linearized rate were 0.3, 0.6 and 1.2%, respectively. No difference was observed for rates of all valve related morbidity: 2.6, 2.4 and 3.5%, respectively. Risk of thromboembolism increased with age, linearized rates were: 0.3, 0.7 and 1.3%. Risk of deterioration and reoperation decreased with age, rates of deterioration were 0.8, 0.1 and 0%. Other valve related events had the same incidence in all groups. No statistical difference was observed between group II and group III for deteriorations and reoperations. CONCLUSIONS: The performance of the Carpentier-Edwards pericardial valve is the same at 10 years in group II and III. This study supports the clinical use of this tissue valve in patients over 60 years. The results in group I are satisfactory, nevertheless, a more durable biological valve is needed for young patients.

Actuarial Analysis↗
PubMed1997

Real time validation of paediatric biochemical reports using the Valab-Biochem system.

Validation of biochemical reports must be fast and clinically accurate to be of assistance to clinicians. Considerable skill is required to analyse the consistency of different data in the report and to consider influences on the data. When performed throughout the day, such analysis is time-consuming and uncertain. We therefore decided to use a computer-assisted validation system, Valab-Biochem. Its decisions result from a decision tree based primarily on the intrinsic consistency of the data, validation ranges and patients' sex, age and hospital ward. Three hundred randomly chosen reports were simultaneously submitted to Valab-Biochem and to five biologists in order to analyse the computer's findings. The sensitivity of Valab-Biochem was 80% compared to biologists' consensus decision, which was taken as the gold standard. The specificity was 78%. This system provided autonomous assessment of the reports and could be used as an initial screen to assist biologists and focus attention on potentially inconsistent reports.

Artificial Intelligence↗