Administration of rituximab during the first trimester of pregnancy without consequences for the newborn.

Rituximab, a chimeric mouse/human monoclonal antibody that binds to the CD20 antigen, is part of current treatment of many B-cell malignancies and several autoimmune diseases. Very few cases of rituximab administration during pregnancy have been described. We report here the case of rituximab administration during the first trimester of pregnancy in a woman with autoimmune hemolytic anemia. No significant effects were observed in B-cell counts or the immune status of the newborn.

Delayed extraction experiments using a repulsing potential before ion extraction: evidence of non-covalent clusters as ion precursor in UV matrix-assisted laser desorption/ionization. Part II--Dynamic effects with alpha-cyano-4-hydroxycinnamic acid matrix.

Delayed extraction experiments were undertaken to gain a better insight into the dynamic effects involved in the ion formation in UV matrix-assisted laser desorption/ionization. Part I1 was devoted to a 2,5-dihydroxybenzoic (2,5-DHB) matrix. The results clearly demonstrated the existence and the role of high-mass precursors corresponding to a non-covalent matrix-analyte association in ion formation. In this complementary study, ion flight time and abundance were studied as a function of the delay extraction time using the matrix alpha-cyano-4-hydroxycinnamic acid (HCCA). Under our instrumental conditions, where ejected ions experienced a low repulsing electric field before extraction, two main results were obtained: (i) two ion components are observed in the peak profiles depending on the repulsing field, a first, major component (I) similar to that observed for 2,5-DHB and a second, minor component (II) apparently triggered by the delayed extraction pulse, and (ii) ion time-of-flight variation vs delay time remained lower than that noted with 2,5-DHB matrix, indicating that the initial axial velocity is smaller. The initial kinetic energy of matrix and low molecular mass peptide ions for the component I is not high enough to overcome the repulsing potential in the delay time range (200-2200 ns) and we have to assume that ions have non-covalent clusters as precursors. Complete desolvation of these clusters-aggregates would be achieved through the extraction step. Simulations of the ion time-of-flight as a function of the delay time allow the determination of the average size of the precursors, typically 4500, 40000 and 50000 u for HCCA, ACTH 7-38 and bovine insulin quasi-molecular ion, respectively, assuming that the precursors are singly charged. The size of these ion precursors is greater than that of those generated for 2,5-DHB. For component II, ions are probably not solvated and they are directly desorbed from the target. Taking into account the results on HCCA and 2,5-DHB matrices and other results from the literature, a general model for ion formation based on clusters as ion precursors is proposed and discussed.

Peripheral blood and BM CD34+ CD38- cells show better resistance to cryopreservation than CD34+ CD38+ cells in autologous stem cell transplantation.

BACKGROUND: We and others have shown a critical role for CD34+ CD38- cells in hematopoietic recovery after autologous stem cell transplantation (ASCT), in particular for platelet reconstitution. Thus a routine assessment of CD34+ CD38- cells in freezing-thawing procedures for autografting could represent an important tool for predicting poor engraftment. METHODS: To compare the impact of cryopreservation on CD34+ CD38+ and CD34+ CD38- hematopoietic stem cell subsets, 193 autograft products collected in 84 patients with malignancies were assessed before controlled-rate cryopreservation in 10% DMSO and after thawing for autografting. RESULTS: Cell counts after thawing were significantly different from the pre-freezing counts for total CD34+ (P<0.0001) and CD34+ CD38+ (P<0.0001) cells, but not for CD34+ CD38- cells (P=0.252). Median losses for CD34+, CD34+ CD38+ and CD34+ CD38- cells were, respectively, 11.8%, 11.4% and 0.0%. The magnitude of fresh/post-thawing percentage cell variation was significantly different when comparing between the CD34+ CD38+ and CD34+ CD38- cell subsets (P<0.001). Moreover, CD34+ CD38- cells exhibited recovery values > or =100% in 85/160 graft products, compared with 51/193 in CD34+ CD38+ cells (P<0.0001). Also, recovery values > or =90% were significantly better in the CD34+ CD38- (98/160 grafts) than in the CD34+ CD38+ subsets (89/193 grafts) (P<0.01). DISCUSSION: In this work we have demonstrated that CD34+ cells that do not express the CD38 Ag show a significantly better resistance to cryopreservation. This could represent another example of the particular ability of less committed progenitor cells to overcome environmental injuries. Moreover, we consider routine assessment of CD34+ CD38- cells before freezing as clinically relevant, but post-thawing controls may be avoided because of their good resistance to freezing.

[Economic repercussions of cardiac insufficiency in France]. / Répercussion économique de l'insuffisance cardiaque en France.

The aim of the article is to review economic and public health consequences of congestive heart failure in France. This disease with an increasing prevalence induces for the social security system and the society a high cost; 85 to 93% of this cost are bound to hospitalizations, most of them avoidable. New modalities of care are to be chosen in order to improve the management of heart failure and to contain costs. In this context, multidisciplinary interventions based on patients' education are experimented taking care to assure a greater role to health actors working in the ambulatory sector (GPs, private cardiologists, nurses).

[Pharmaco-epidemiological study on antipsychotic drug prescription in French Psychiatry: Patient characteristics, antipsychotic treatment, and care management for schizophrenia]. / Etude pharmaco-épidémiologique de la prescription des antipsychotiques en milieu psychiatrique en France -

UNLABELLED: In 2000, a one week national survey was conducted among 202 psychiatrists (129 participants) in France, from hospitals and clinics, private or public. The first 20 inpatients and 10 outpatients prescribed at least one antipsychotic drug (age range 18-65), were included. The diagnostic procedure was standardized with a structured interview: the Mini International Neuropsychiatric Interview (MINI). A total 2 068 patients were included, among whom 892 (43.1%) reached the criteria of schizophrenia according ICD-10. We present here data on these latter patients. Mean age was 38.8 years; with 38.8% females. Median duration of current antipsychotic treatment was 0.5 year in inpatients and 2 years in outpatients. Median duration of any antipsychotic treatment was 10 years, without difference between groups. Comorbid situations (anxiety disorder, depression and suicidal risk) were found in 33.1% of schizophrenic patients, with higher frequency among inpatients in private hospitals (54.8%) than in other groups. 46.8% patients were prescribed at least 2 neuroleptics, and 73.6% at least one non-neuroleptic drugs. Cyamemazine accounted for 16.6% of all neuroleptics drugs, and 56% of patients were prescribed an atypical antipsychotic (risperidone, olanzapine, amisulpride or clozapine). Atypical drugs accounted for 59.4% of patients who were prescribed only one neuroleptic drug. Inpatients had more neuroleptics coprescription than outpatients (mean 1.8 vs 1.4 drugs), with higher daily dose. In addition, inpatients had more other psychotropics prescribed (mean 1.5 vs 1.1 drugs). Overall, more other psychotropic drugs were prescribed among patients with -, than those without - comorbid situations (1.7 vs 1.2 drugs). Median time since admission, at the time of the study, were similar in private and public hospitals (107 vs 99 days) but maximal time since admission was respectively 2.8 and 48.9 years. Visit frequency for outpatients was more than one every two weeks for 43.1% in private and 24.7% in public clinics. Among inpatients only we found a difference between private and public hospitals for polypharmacy of non neuroleptics psychotropics, (mean 1.9 vs 1.5). In outpatients, long acting depot accounted for 26.6% of neuroleptics treatments in public clinics and 15.4% in private clinics. Finally, we found that polypharmacy among outpatients increased with duration of antipsychotic treatment. CONCLUSION: in France, important differences are reported in antipsychotic prescription for schizophrenia between in- and outpatients. Current antipsychotic prescription is more recent in inpatients than in outpatients, with similar duration of overall antipsychotic treatment. Inpatients have more drug prescription, antipsychotics and other psychotropics, than outpatients. Differences are less important between private and public providers. Inpatients in private hospitals receive more non neuroleptic drugs than in public hospitals, and depot antipsychotics are more used among patients of public clinics. Long term inpatients are found in public hospitals only. Outpatients follow up is more intensive in private than in public clinics.

High-pressure ion source combined with an in-axis ion trap mass spectrometer. 1. Instrumentation and applications

A new combination of a dual EI/CI ion source with a quadrupole ion trap mass spectrometer has been realized in order to efficiently produce negative ions in the reaction cell. Analysis of volatile compounds was performed under negative ion chemical ionization (NICI) during a reaction period where selected reactant negative ions, previously produced in the external ion source, were allowed to interact with molecules, introduced by hyphenated techniques such as gas chromatography. The O2*-, CH3O-, and Cl- reactant ions were used in this study to ensure specific ion/molecule interactions such as proton transfer, nucleophilic displacement, or charge exchange processes, respectively leading to even-electron species, i.e., deprotonated [M - H]- molecules, diagnostic [M - R]- ions, or odd-electron M*- molecular species. The reaction orientation depends on the thermochemistry of reactions within kinetic controls. First analytical results are presented here for the trace-level detection of several contaminants under NICI/Cl- conditions. Phosphorus-containing compounds (malathion, ethyl parathion, and methyl parathion as representative for pesticides) and nitro-containing compounds (2,4,6-trinitrotoluene for explosive material) have been chosen in order to explore the analytical ability of this promising instrumental coupling.

High-pressure ion source combined with an in-axis ion trap mass spectrometer. 2. Application of selective low-pressure negative ion chemical ionization

Negative ion chemical ionization was carried out using a quadrupole ion trap mass spectrometer with selected reactant negative ions, primarily injected from a homemade dual EI/CI external ion source. Hence, selective ion/molecule reactions were provided according to the reaction time, which induce a greater control over bimolecular ionization mechanisms than in conventional a high-pressure ion source combined with beam instruments, where several competitive ionization processes take place mainly due to source conditions (e.g., temperature, pressure, and repeller). By selecting the reactant ions, ion/molecule reactions were specifically produced (i.e., charge exchange, proton transfer, nucleophilic substitution, and/or alpha-beta elimination) with several organic target compounds. Gas-phase reactivity of phosphorus- and nitrogen-containing compounds (such as phosphonates as representative for chemical warfare agents and phosphorothionates, phosphorodithionates, and triazines for pesticides) as well as dinitro aromatic compounds (for pesticides) has been explored, in the present work, to ensure further unambiguous detection.

Sodium ion attachment reactions in an ion trap mass spectrometer

The capabilities of ion traps to perform attachment reactions with alkali cations using classical scanning sequences have been exploited here with an ion trap mass spectrometer equipped with an external ion source to generate the reagent Na(+) ions. Kinetic studies have shown that, as expected, the attachment efficiency is very high, near-collision efficiency, and illustrate how the present method is particularly well suited for ion trap mass spectrometers. The large adaptability of the experimental conditions suggests that a wide range of organic molecules, characterized by a large alkali ion affinity, could be readily detected even at low levels. Applications of sodium ion attachment reactions are illustrated by the detection and characterization of explosives and some of their correlated pyrolytic degradation products. Detection -limits for phthalate compounds are shown to reach the low ng range of injected samples, without any noticeable difficulties in the full scan mode of acquiring mass spectra. Copyright 2000 John Wiley & Sons, Ltd.

Coupling of MALDI-TOF mass analysis to the separation of biotinylated peptides by magnetic streptavidin beads.

Extraction of biotinylated peptides by streptavidin magnetic beads has been directly coupled to the MALDI-TOF mass analysis. The elution of peptides from the beads is achieved by first mixing the beads with the MALDI matrix solution and removing, after a few minutes, the beads with a magnet; then, the matrix solution containing the biotinylated peptide is directly mass analyzed by MALDI. Three examples are presented to show the capabilities of this procedure to detect biotinylated peptides present at very low concentrations in complex mixtures. Detection limits of less than 100 finol can be achieved. Such a coupling strategy is of great interest to investigate peptide/ protein interactions.

Failure to detect spindle-shaped fibroblastoid cell progenitors in PBPC collections.

We assessed the development of an adherent stromal layer in peripheral blood progenitor cells (PBPC) collections of 17 patients with solid tumors and hematological malignancies (n = 38), as well as in normal and disease-free bone marrow samples (n = 14). Light-density mononuclear cells from peripheral blood leukapheresis maintained in long term culture (LTC) conditions for at least 3 weeks failed to develop a stromal layer as was observed in all bone marrow samples. We found no differences with regard to CFU-GM growth, CD34+ percentage or cytological morphology. Our results indicate that spindle-shaped fibroblastoid cell progenitors present in the bone marrow are not mobilized towards peripheral blood by chemotherapy and/or growth factor stimulation, contrasting with hematopoietic progenitors, which, as is well known, are able to circulate. The absence of stromal progenitors in PBPC autografts does not appear to be relevant for a successful hematopoietic engraftment.