Prospective multicentric molecular study for poor prognosis fusion transcripts at diagnosis in adult B-lineage ALL patients: the LALA 94 experience.
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Biomedical subjects
Publications and source records attributed to M Dupont.
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Guidelines recommend high doses of beta-lactams for the therapy of endocarditis. This report describes a retrospective study of 15 endocarditis patients (median age 64 years), treated according to guidelines, whose beta-lactam trough plasma concentrations were measured with high-performance liquid chromatography because of tolerance or efficacy concerns. For amoxycillin, the mean level was 86.8 mg/L (range: 30-212 mg/L); five (45%) patients had concentrations > 1000 x MIC. For cloxacillin, the mean level was 47.9 mg/L (range: 16.7-104 mg/L). The consequences of high and unpredicted beta-lactam trough plasma concentrations for a prolonged period have not yet been thoroughly evaluated.
Air conditioning and dehumidifying systems based on sorption on solids are of great interest, especially in humid climates, because they allow reduction of thermal loads and use of chlorofluorocarbons. Previous studies have shown that hydrophilic polymers such as sulfonic polymers can have very high performance in water adsorption from air. The aim of this study was to characterize the water vapor adsorption properties of fully sulfonated and monosulfonated poly(styrenesulfonic acid), sodium salt, and to elucidate the mechanism of adsorption on these materials. Adsorption isotherms have been determined by TGA between 298 and 317 K for pressures ranging from 0.1 to 45 hPa. They have type II of the IUPAC classification and a small hysteresis loop between adsorption and desorption processes was observed only for the monosulfonated sample. Water content is up to 80% weight at 80% relative humidity. Adsorption isotherms have been well fitted with the FHH model. Adsorption-desorption isobars have been determined by TGA under 37 hPa in the temperature range 298-373 K. They show that these polymers can be completely regenerated by heating at 313 K under humidified air. No degradation of the adsorption properties has been observed after several regenerations. Adsorption enthalpies and entropies have been deduced from the Clapeyron equation and from DSC measurements. A good agreement was found. A mechanism of adsorption is proposed considering two kinds of adsorbate: bounded water in electrostatic interaction with functional groups and free water resulting from condensation.
INTRODUCTION: There is little information on the frequency, physiopathology and management of extra-cerebral manifestations of N. meningitidis meningitis. Articular, pleural and pericardial involvement is occasionally reported with a symptomatology that can be delayed with regard to the initial diagnosis. OBSERVATIONS: In two patients in whom the diagnosis of meningococcal meningitis had been confirmed, the progression was towards a recurrent pericarditis up until the 4th month after the initial episode of infection in the first case and pericarditis with tamponade and surgical draining in the second. However, the final outcome was favourable for both patients following treatment with non-steroidal anti-inflammatories (NSAIs). COMMENTS: The incidence of pericardial involvement is unknown. The distinction has to be made between purulent pericarditis, more frequent in children, and the inflammatory pericarditis that is often of late onset. The indication for surgical draining must be dominated by the clinical hemodynamic impact. The indication for NSAIs and/or acetyl-salicylic acid is not codified (doses, duration), but in the two cases reported here we would privilege NSAIs.
BACKGROUND: Postoperative bladder distension and urinary retention are commonly underestimated. Ultrasound enables accurate measurement of bladder volume and thus makes it possible to determine the prevalence of postoperative bladder distension. METHODS: Using ultrasound, we measured the volume of the bladder contents at the time of discharge from the recovery room in 177 adult patients who had undergone thoracic, vascular, abdominal, orthopaedic or ENT surgery. RESULTS: Forty-four per cent of the patients had a bladder volume >500 ml and 54% of the 44%, who had no symptoms of bladder distension, were unable to void spontaneously within 30 min. The risk factors for urinary retention were age >60 yr (odds ratio (OR) 2.11, 95% confidence interval (CI) 1.01-4.38), spinal anaesthesia (OR 3.97, 95% CI 1.32-11.89) and duration of surgery >120 min (OR 3.03, 95% CI 1.39-6.61). CONCLUSION: Before discharge from the recovery room it seems worthwhile to systematically check the bladder volume with a portable ultrasound device in patients with risk factors.
OBJECTIVES: To analyze the frequency of systemic factors leading to secondary brain insults in victims of serious head trauma in a prehospital setting and to evaluate a protocol for the advanced prehospital emergency care by mobile intensive care unit (i.e., the French Samu-Smur system). STUDY DESIGN: Prospective study, over a period of 24 months. PATIENTS AND METHODS: This prospective study involved 60 victims of severe head injuries (with the exception of polytrauma patients). Tracheal intubation was performed on each patient under direct laryngoscopy and after induction of anaesthesia (fentanyl-etomidate-rocuronium). Controlled ventilation and vascular loading (objectives: SpO(2) >or= 97%, PETCO(2) between 30 and 35 mmHg, SAP >or= 90 mmHg) were administered. RESULTS: Hypoxaemia was found to be the most frequent cause of secondary insults (57% of patients with SpO(2) < 97%). In the case involving an accident that occurred 17 km from the hospital (with extremes of 6-65 km), the speed of medical intervention was note-worthy: tracheal intubation was performed 50 min after the accident, and the patient was admitted into a trauma centre 101 min after impact (median). However, faster intervention could be obtained if the transmission of the alert was improved. The conditions under which the tracheal intubation was performed were found to be satisfactory (difficult intubation 1.6%) without deteriorating the haemodynamic status. This is probably related to the use of muscle relaxants and the choice of etomidate as the first line hypnotic in the prehospital emergency care.
Reciprocal rearrangements of the MLL gene are among the most common chromosomal abnormalities in both Acute Lymphoblastic and Myeloid Leukemia. The MLL gene, located on the 11q23 chromosomal band, is involved in more than 40 recurrent translocations. In the present study, we describe the development and validation of a biochip-based assay designed to provide a comprehensive molecular analysis of MLL rearrangements when used in a standard clinical pathology laboratory. A retrospective blind study was run with cell lines (n=5), and MLL positive and negative patient samples (n=31), to evaluate assay performance. The limits of detection determined on cell line data were 10(-1), and the precision studies yielded 100% repeatability and 98% reproducibility. The study shows that the device can detect frequent (AF4, AF6, AF10, ELL or ENL) as well as rare partner genes (AF17, MSF). The identified fusion transcripts can then be used as molecular phenotypic markers of disease for the precise evaluation of minimal residual disease by RQ-PCR. This biochip-based molecular diagnostic tool allows, in a single experiment, rapid and accurate identification of MLL gene rearrangements among 32 different fusion gene (FG) partners, precise breakpoint positioning and comprehensive screening of all currently characterized MLL FGs.
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The detection of chimeric transcripts derived from aberrant chromosomal fusion events provides an exceptionally valuable toolfor the diagnosis of leukemia. We have developed a simple, inexpensive, reproducible, and automated method to quantify RT-PCR products. Our approach utilizesfluorescent PCRfor the co-ampification of the specific fusion transcript with an internal control (HPRT). We have also combined the advantages of real-time quantitative PCR, namely continuous fluorescent detection of PCR products with the low cost of an endpoint assay by examining in a novel manner the amount offluorescent PCR product generated during the exponential phase of amplification. This has been achieved by using the automated loading and quantification capacity of a laser-induced fluorescence capillary electrophoresis system, the ABI PRIsMS 310A, so that we can effectively monitor amplification during the exponential phase cheaply, reproducibly, and in a sensitive manner. We have carefully verified our new technique using five leukemia cell lines, each expressing a differentfusion transcript. Specificity and reproducibility (cy within 10%) have been examined and demonstrate the excellent precision of our technology. The high sensitivity levels of at least 10(-4) to 10(-6) obtainedfor the serial dilutions of the five cell lines validate the choice of our fluorescent PCR as a comparable method to other more complicated and expensive methods. Our results have allowed us to quantify PCR products and the amount of chimeric mRNA originating from the translocation breakpoint. We demonstrate that our novelfluorescent method is useful to detect and quantify residual leukemic cells in patients undergoing therapy.
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INTRODUCTION: In Denmark most IUDs are inserted by general practitioners (GPs). The aim of this study was to throw light on which women choose IUD, the procedure used, and difficulties associated with insertion. MATERIAL AND METHODS: All 232 GPs in Frederiksborg County were invited to participate and 88 agreed. The GP filled in a questionnaire concerning the type of IUD, the age, parity, etc, of the woman and information about the insertion. RESULTS: Eighty-eight GPs contributed with 562 IUD insertions. IUD was mostly used by women above 25 years of age and by women who had given birth to a child. There were no differences in the insertion procedures used by the doctors. Fifty-nine per cent of the women were previous IUD users. Of the former users, 37% reported problems with the previous use of the IUD. Twenty-five per cent of the women in this study reported that they had had heavy or long-lasting menstruation before insertion. Fifty-five per cent of the women had a test for chlamydia before insertion. Twenty-three (4.1%) insertions were abandoned. 26 (4.6%) insertions were described as difficult. The highest frequency was in women using gestagen-releasing IUDs. CONCLUSION: IUD was mainly used by women, who had given birth to a child. The gestagen releasing IUD was mostly used by the elder group and by women with heavy bleedings before insertion. The procedure was very identical and the number of abandoned and difficult insertions were low and only related to the type of IUD. More female than male doctors participated. Doctors working in partnerships participated more frequently than doctors working alone.
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Enterobacter cloacae strain EM was isolated from a commercial dietary mineral supplement stabilized by a mixture of methylparaben and propylparaben. It harbored a high-molecular-weight plasmid and was resistant to high concentrations of parabens. Strain EM was able to grow in liquid media containing similar amounts of parabens as found in the mineral supplement (1,700 and 180 mg of methyl and propylparaben, respectively, per liter or 11.2 and 1.0 mM) and in very high concentrations of methylparaben (3,000 mg liter(-1), or 19.7 mM). This strain was able to hydrolyze approximately 500 mg of methyl-, ethyl-, or propylparaben liter(-1) (3 mM) in less than 2 h in liquid culture, and the supernatant of a sonicated culture, after a 30-fold dilution, was able to hydrolyze 1,000 mg of methylparaben liter(-1) (6.6 mM) in 15 min. The first step of paraben degradation was the hydrolysis of the ester bond to produce 4-hydroxybenzoic acid, followed by a decarboxylation step to produce phenol under aerobic conditions. The transformation of 4-hydroxybenzoic acid into phenol was stoichiometric. The conversion of approximately 500 mg of parabens liter(-1) (3 mM) to phenol in liquid culture was completed within 5 h without significant hindrance to the growth of strain EM, while higher concentrations of parabens partially inhibited its growth.
The 94-654 law (dated 29th July 1994) has modified the french regulation on post-mortem sampling on a deceased person, performed for scientific reasons. The patient's permission has been made mandatory for every autopsy (with the exception of forensic medecine). The permission can be presumed when the autopsy is performed to find the cause of death. In all other cases, the patient's wish must have been expressly signified before death, or testified by his family. In any case, the patient's relative must be informed of the sampling. This law seems to be one reason for the very perceptible decrease of the number of autopsies performed in hospitals these last years.
A thermostability screening assay was developed using an Escherichia coli expression system to express Streptomyces lividans xylanase A (XlnA). The screening system was tested using mutants randomized at position 49 of the S. lividans XlnA gene, a position previously shown to confer thermostability with a I49P point mutation. The library was cloned into an E. coli expression vector and transformed into XL1-blue bacteria. The resulting clones were screened for increased thermostability with respect to wild-type XlnA. Using this assay, we isolated the I49P mutant previously shown to be thermostable, as well as novel I49A and I49C mutants. The I49A and I49C mutants were shown to have 2.8- to 8-fold increase in thermostability over that of wild-type XlnA. The results show that the screening assay can selectively enrich for clones with increased thermostability and is suitable for screening small- to medium-sized libraries of 5000-20,000 clones.
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We report on the molecular characterization of two acute myeloid leukemias (AML), one AML-M1 (patient 1) and one AML-M2 (patient 2) with t(8;21)(p21;q22) and t(8;20)(q22;p13), respectively, at diagnosis. The locations of the breakpoints, 21q22 in patient 1 and 8q22 in patient 2, prompted us to search for a cryptic t(8;21)(q22;q22) and involvement of the AML1 and ETO genes. Dual-color fluorescence in situ hybridization (FISH) using whole chromosome painting probes for chromosomes 8, 20, and 21 confirmed the conventional cytogenetic karyotypes. However, dual-color FISH using appropriate ETO and AML1 probes disclosed an insertion of AML1 into 8q22 on the derivative chromosome 8 in patient 1 and of ETO into 21q22 on one chromosome 21 in patient 2, leading to AML1-ETO fusion signals. Both cases expressed an AML1-ETO transcript, shown by reverse transcriptase polymerase chain reaction and cDNA sequencing. Creation of functional AML1-ETO fusion genes in these two simple variant t(8;21) probably occurred through complex mechanisms, combining translocation and insertion of chromosomal segments.