Re: Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas.
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Chlamydia Infections↗
Biomedical subjects
Philippe Arnaud
Publications and source records attributed to Philippe Arnaud.
Comparison of hydrogen peroxide and peracetic acid as isolator sterilization agents in a hospital pharmacy.
PURPOSE: The efficacy of hydrogen peroxide and peracetic acid as isolator sterilization agents was compared. METHODS: Sterilization and efficacy tests were conducted in a flexible 0.8-m3 transfer isolator using a standard load of glass bottles and sterile medical devices in their packing paper. Bacillus stearothermophilus spores were placed in six critical locations of the isolator and incubated at 55 degrees C in a culture medium for 14 days. Sterilization by 4.25 mL/m3 of 33% vapor-phase hydrogen peroxide and 12.5 mL/m3 of 3.5% peracetic acid was tested in triplicate. Sterility was validated for hydrogen peroxide and peracetic acid at 60, 90, 120, and 180 minutes and at 90, 120, 150, 180, 210, and 240 minutes, respectively. RESULTS: In an efficacy test conducted with an empty isolator, the sterilization time required to destroy B. stearothermophilus spores was 90 minutes for both sterilants, indicating that they have comparable bactericidal properties. During the validation test with a standard load, the sterilization time using hydrogen peroxide was 150 minutes versus 120 minutes with peracetic acid. The glove cuff was particularly difficult for hydrogen peroxide to sterilize, likely due to its slower diffusion time than that of peracetic acid. Hydrogen peroxide is an environmentally safer agent than peracetic acid; however, its bacteriostatic properties, lack of odor, and poor diffusion time may limit its use in sterilizing some materials. CONCLUSION: Hydrogen peroxide is a useful alternative to peracetic acid for isolator sterilization in a hospital pharmacy or parenteral nutrition preparation unit.
Disinfectants↗
MEDEA takes control of its own imprinting.
Genomic imprinting is an essential epigenetic process that controls the size of seeds in flowering plants. In Arabidopsis, DEMETER activates the maternal copy of the imprinted MEDEA Polycomb gene. In this issue of Cell, Gehring et al. (2006) demonstrate that this activation involves DNA demethylation of MEDEA by DEMETER. Remarkably, they also find that silencing of the paternal MEDEA allele is independent of DNA methylation and is controlled by maternal expression of MEDEA itself.
Animals↗
Stochastic imprinting in the progeny of Dnmt3L-/- females.
The cis-acting regulatory sequences of imprinted genes are subject to germline-specific epigenetic modifications, the imprints, so that this class of genes is exclusively expressed from either the paternal or maternal allele in offspring. How genes are differentially marked in the germlines remains largely to be elucidated. Although the exact nature of the mark is not fully known, DNA methylation [at differentially methylated regions (DMRs)] appears to be a major, functional component. Recent data in mice indicate that Dnmt3a, an enzyme with de novo DNA methyltransferase activity, and the related protein Dnmt3L are required for methylation of imprinted loci in germ cells. Maternal methylation imprints, in particular, are strictly dependent on the presence of Dnmt3L. Here, we show that, unexpectedly, methylation imprints can be present in some progeny of Dnmt3L(-/-) females. This incomplete penetrance of the effect of Dnmt3L deficiency in oocytes is neither embryo nor locus specific, but stochastic. We establish that, when it occurs, methylation is present in both embryo and extra-embryonic tissues and results in a functional imprint. This suggests that this maternal methylation is inherited, directly or indirectly, from the gamete. Our results indicate that in the absence of Dnmt3L, factors such as Dnmt3a and possibly others can act alone to mark individual DMRs. However, establishment of appropriate maternal imprints at all loci does require a combination of all factors. This observation can provide a basis to understand mechanisms involved in some sporadic cases of imprinting-related diseases and polymorphic imprinting in human.
Animals↗
Effect of chitosan-coated alginate microspheres on the permeability of Caco-2 cell monolayers.
Alginate microspheres were prepared by emulsification/internal gelation and coated with chitosan. The ability of chitosan-coated alginate microspheres to increase the paracellular transport across Caco-2 cell monolayers was evaluated in comparison to uncoated microspheres and chitosan solutions. Transport studies were performed by using a permeability marker, Lucifer Yellow (LY), and by measuring the transepithelial electric resistance (TEER) variations. Furthermore, the occurrence of cytotoxic effects was assessed by evaluating neutral red uptake in viable cells and lactate dehydrogenase (LDH) release from damaged cells. A 3-fold increase on LY permeability was obtained for coated microspheres when compared to chitosan solutions. TEER variations were in agreement with permeability results. Chitosan solutions exhibited a dose-dependent toxicity, but coated microspheres did not decrease the viability of cells. Chitosan-coated alginate microspheres have potential to be used as carriers of poorly absorbable hydrophilic drugs to the intestinal epithelia and possibly increase their oral bioavailability.
Alginates↗
Conjunctival low-grade non-Hodgkin's lymphoma: a large single-center study of initial characteristics, natural history and prognostic factors.
To define the initial characteristics and prognostic factors of patients with conjunctival low-grade malignant lymphoma, all patients treated for low-grade lymphoma with initial conjunctival involvement were reviewed. Forty-nine cases were selected, including 45 cases with exclusive ophthalmologic conjunctival involvement. Pathologic review showed 55% of mucosa-associated lymphoid tissue type lymphoma, and 23% of lymphoplasmocytic lymphoma. Initial characteristics were median age of 62 years, nodal involvement in 17% of cases, and stage IV in 22% of patients with 10% of bone marrow involvement. With a median follow-up of 75 months, the 5-year disease-free survival (DFS) and overall survival were 65% and 83%, respectively. On multivariate analysis, nodal involvement was the only factor with a pejorative impact on DFS. Our patient cohort represents one of the largest published series defining the characteristics and prognostic factors of primary conjunctival low-grade malignant lymphoma.
Age Factors↗
High efficacy of combined rituximab and gemcitabine on Epstein-Barr virus-associated human B-cell lymphoma obtained after Hodgkin's xenograft in immunodeficient mice.
The objectives were to characterize an Epstein-Barr virus-associated human B-cell lymphoma obtained from Hodgkin's xenograft, and to evaluate the in-vivo combination of rituximab and/or gemcitabine. A lymph node biopsy sample from a patient with Hodgkin's disease was xenografted into Rag gamma(c)(-/-) mice. Immunohistochemical, cytogenetic and genetic analyses were performed on both the human biopsy and xenografted tumor from severe combined immunodeficient mice. Tumor-bearing mice were then treated with rituximab and/or gemcitabine. Histologic features of the patient's biopsy concluded on classical CD15/CD30-positive Hodgkin's disease without expression of Epstein-Barr virus proteins. In contrast, morphologic and immunophenotypic examination of the xenograft showed diffuse proliferation of large B cells with high Epstein-Barr virus protein expression. Comparative genomic hybridization showed a normal pattern in the first case and a gain of chromosomal 12 in the xenografted tumor. Finally, polymerase chain reaction detected an immunoglobulin heavy chain rearrangement in the xenografted tumor. Altogether, these results indicate that the xenograft grew from the patient's Epstein-Barr virus-infected B-lymphoid cells and could be assimilated to posttransplant lymphoproliferative disease. In-vivo treatments of xenografted tumors showed significant tumor growth inhibition induced either by rituximab or gemcitabine alone and an impressive efficacy of combined treatment. This result therefore indicates that combined rituximab and gemcitabine could be an alternative approach in patients with posttransplant lymphoproliferative disease.
Adult↗
Outcome of critically ill allogeneic hematopoietic stem-cell transplantation recipients: a reappraisal of indications for organ failure supports.
PURPOSE: Because the overall outcome of critically ill hematologic patients has improved, we evaluated the short-term and long-term outcomes of the poor risk subgroup of allogeneic hematopoietic stem-cell transplantation (HSCT) recipients requiring admission to the intensive care unit (ICU). PATIENTS AND METHODS: This was a retrospective multicenter study of allogeneic HSCT recipients admitted to the ICU between 1997 and 2003. RESULTS: Two hundred nine critically ill allogeneic HSCT recipients were included in the study. Admission in the ICU occurred during the engraftment period (< or = 30 days after transplantation) for 70 of the patients and after the engraftment period for 139 patients. The overall in-ICU, in-hospital, 6-month, and 1-year survival rates were 48.3%, 32.5%, 27.2%, and 21%, respectively. Mechanical ventilation was required in 122 patients and led to a dramatic decrease in survival rates, resulting in in-ICU, in-hospital, 6-month, and 1-year survival rates of 18%, 15.6%, 14%, and 10.6%, respectively. Mechanical ventilation, elevated bilirubin level, and corticosteroid treatment for the indication of active graft-versus-host disease (GVHD) were independent predictors of death in the whole cohort. In the subgroup of patients requiring mechanical ventilation, associated organ failures, such as shock and liver dysfunction, were independent predictors of death. ICU admission during engraftment period was associated with acceptable outcome in mechanically ventilated patients, whereas patients with late complications of HSCT in the setting of active GVHD had a poor outcome. CONCLUSION: Extensive unlimited intensive care support is justified for allogeneic HSCT recipients with complications occurring during the engraftment period. Conversely, initiation or maintenance of mechanical ventilation is questionable in the setting of active GVHD.
Acute Disease↗
Evidence for a basal release of a cytochrome-related endothelium-derived hyperpolarizing factor in the radial artery in humans.
Whether a cytochrome P-450 (CYP)-related endothelium-derived hyperpolarizing factor (EDHF), acting through calcium-activated potassium (K(Ca)) channels, interacts with nitric oxide (NO) to regulate the basal diameter of human peripheral conduit arteries is unexplored in vivo. Radial artery diameter (echo tracking) and blood flow (Doppler) were measured, after oral aspirin (500 mg), in eight healthy volunteers during local infusion for 8 min of tetraethylammonium chloride (TEA; 9 micromol/min), as K(Ca) channel inhibitor, and fluconazole (0.4 micromol/min), as CYP inhibitor, alone and in combination with N(G)-monomethyl-L-arginine (L-NMMA; 8 micromol/min), as endothelial NO synthase inhibitor. Endothelium-independent dilatation was assessed by using sodium nitroprusside (SNP). Radial diameter was unaffected by L-NMMA (0.4 +/- 0.9%) and fluconazole (-1.6 +/- 0.8%) but was decreased by TEA (-5.0 +/- 1.0%), L-NMMA + fluconazole (-5.3 +/- 0.5%), and L-NMMA + TEA (-9.9 +/- 1.3%). These effects are still significant even when the concomitant decreases in blood flow induced by L-NMMA (-24 +/- 4%), TEA (-21 +/- 3%), L-NMMA + fluconazole (-26 +/- 5%), and L-NMMA + TEA (-35 +/- 4%) were taken as covariate into analysis. Conversely, fluconazole alone slightly but not significantly increased radial flow (13 +/- 6%). L-NMMA alone or with TEA and with fluconazole enhanced radial artery dilatation to SNP, whereas TEA and fluconazole alone did not modify this response. These results confirm in humans the involvement of NO and K(Ca) channels in the regulation of basal conduit artery diameter. Moreover, the synergistic effect of combined inhibition of NO synthesis and CYP on the decrease in radial diameter in the absence of such effect after L-NMMA and fluconazole alone unmasks the role of CYP in this regulation and shows the presence of an interaction between NO and a CYP-related EDHF to maintain peripheral conduit artery diameter in vivo. Furthermore, the higher vasoconstrictor effect of TEA compared with fluconazole suggests that different K(Ca) channel-dependent hyperpolarizing mechanisms could exist in conduit arteries.
Adult↗
Development of cyclodextrin microspheres for pulmonary drug delivery.
PURPOSE: Microparticles of diameter < 5 microm were synthesized by interfacial cross-linking of 7.5% (w/v) beta-cyclodextrins (beta-CD) with 4.5% (w/v) terephtaloyle chloride in 1 M NaOH, in order to provide stable vector for drug encapsulation suitable for administration at the alveolar scale. METHODS: Batches were prepared varying different parameters such as amount of monomer (beta-CD) (5-30% w/v), NaOH concentration (0.5-4 M), reaction time (15-240 min), agitation rate (8000-24000 rpm), amount of cross-linking agent (terephtaloyle chloride: 1.25-10% w/v), surfactant percentage (2.5-10% of Span 85), studying the influence of the freeze-drying step. Microparticles were controlled with respect to their size by a laser diffraction technique, pH of the colloidal suspension, IR spectroscopy, Differential Scanning Calorimetry. After optimization of the microparticles size, complexation with amikacin sulfate was investigated comparing encapsulation efficiency and yield at each step of the preparation (solubilization, emulsification, cross-linking, freeze-drying), contact time and influence of the amount of amikacin. RESULTS: An optimized method was obtained with 1 M NaOH, 4.5% (w/v) cross-linking agent and 5% (w/v) surfactant agent, a 30 min reaction time, a 24000 rpm agitation rate, conducting to microparticles whose size is inferior to 5 microm. Amikacin sulfate encapsulation in polycondensed beta-cyclodextrin showed that better incorporation was obtained during the solubilization step or just before freeze-drying. CONCLUSIONS: Amikacin encapsulation in 5 microm diameter microparticles of beta-CD is achievable for pulmonary drug delivery.
Administration, Inhalation↗
Calcium-activated potassium channels and NO regulate human peripheral conduit artery mechanics.
The role of NO in the regulation of the mechanical properties of conduit arteries is controversial in humans, and the involvement of an endothelium-derived hyperpolarizing factor (EDHF), acting through calcium-activated potassium (KCa) channels, has never been investigated at this level in vivo. We assessed in healthy volunteers, after oral administration of aspirin (500 mg), the effect of local infusion of NG-monomethyl-L-arginine (L-NMMA; 8 mumol/min for 8 minutes), an NO synthase inhibitor, tetraethylammonium chloride (TEA; 9 mumol/min for 8 minutes), a KCa channels inhibitor, and the combination of both on radial artery internal diameter, wall thickness (echo tracking), blood flow (Doppler), and pressure. The incremental elastic modulus and compliance were fitted as functions of midwall stress. L-NMMA decreased modulus and increased compliance at high levels of midwall stress (all P<0.05) without affecting radial diameter. TEA reduced radial diameter from 2.68+/-0.07 to 2.50+/-0.08 10(-3) m, increased the modulus, and decreased the compliance at all levels of stress (all P<0.05). Combination of both inhibitors synergistically enhanced the increase in modulus, the decrease in diameter (from 2.71+/-0.10 to 2.42+/-0.09 10(-3) m), and compliance compared with TEA alone (all P<0.05). These results confirm that inhibition of NO synthesis is associated with a paradoxical isometric smooth muscle relaxation of the radial artery. They demonstrate the involvement of KCa channels in the regulation of the mechanical properties of peripheral conduit arteries, supporting a role for EDHF at this level in vivo. Moreover, the synergistic effect of l-NMMA and TEA shows that KCa channels compensate for the loss of NO synthesis to maintain peripheral conduit artery diameter and mechanics.
Adult↗
Intensive chemotherapy with mitoxantrone administered as a single injection in patients with high-risk acute myeloid leukemia: results of the EMA 2000 trial.
Following a dose-escalation study performed to assess the maximally tolerated dose of high-dose mitoxantrone in a single injection combined with chemotherapy, a phase II trial (EMA 2000 regimen) was performed in patients with refractory or relapsed acute myelogenous leukemia (AML) between October 2000 and December 2003. Sixty-two patients entered the study and received mitoxantrone 45 mg/m(2) on day 1 in combination with cytarabine and etoposide. Overall, 39 patients (63%) achieved complete remission (CR). Four patients died during remission induction, and 19 patients had resistant disease. Median time to granulocyte and platelet recovery was 34 and 39 days, respectively. The predominant non-hematologic toxicity was infection, with 53% severe infections. Thirty-three of the 39 remitters received subsequent treatment consisting of maintenance chemotherapy courses in 17 patients, allogeneic stem cell transplantation (SCT) in 7 patients, and autologous SCT in 9 patients. The median overall survival of the entire cohort was 8.1 months, with 18% at 2.5 years. EMA chemotherapy using a single injection of mitoxantrone is effective in the treatment of high-risk AML. CR proportion was significantly higher in patients with a first CR duration > or =6 months when compared with those from a control trial using standard-dose mitoxantrone (90 vs 70%, p=0.03).
Acute Disease↗
Epigenetic deregulation of genomic imprinting in human disorders and following assisted reproduction.
Imprinted genes play important roles in the regulation of growth and development, and several have been shown to influence behavior. Their allele-specific expression depends on inheritance from either the mother or the father, and is regulated by "imprinting control regions" (ICRs). ICRs are controlled by DNA methylation, which is present on one of the two parental alleles only. These allelic methylation marks are established in either the female or the male germline, following the erasure of preexisting DNA methylation in the primordial germ cells. After fertilization, the allelic DNA methylation at ICRs is maintained in all somatic cells of the developing embryo. This epigenetic "life cycle" of imprinting (germline erasure, germline establishment, and somatic maintenance) can be disrupted in several human diseases, including Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS), Angelman syndrome and Hydatidiform mole. In the neurodevelopmental Rett syndrome, the way the ICR mediates imprinted expression is perturbed. Recent studies indicate that assisted reproduction technologies (ART) can sometimes affect the epigenetic cycle of imprinting as well, and that this gives rise to imprinting disease syndromes. This finding warrants careful monitoring of the epigenetic effects, and absolute risks, of currently used and novel reproduction technologies.
Alleles↗
Usability study on two handheld computers to retrieve drug information.
UNLABELLED: Objective :Performing a usability study on two handheld computers (personal digital assistant and tablet PC), as tools for retrieving drug information. MATERIALS AND METHODS: A randomised crossover study was performed: 34 students in pharmacy and medicine used the two handheld tools in a randomised order, to answer a questionnaire containing 12 questions covering all the aspects of a drug database and a qualitative analysis on six different items to measure access to drug information. The availability of the drug information database Vidal on PDA and on tablet PC implied our choice of the database. Three main criteria for evaluation were chosen: success rates, time-on-task, and number of clicks. RESULTS: There were no significant differences between the two groups neither on age, sex, medical discipline, study years nor previous computer practice. The success rate is significantly higher with the PDA for only one question. The PDA is significantly faster than the tablet PC on 7 of the 12 questions and generates fewer clicks for 3 questions. Compared to the tablet PC, it appears that the PDA is better in terms of clearness, navigability and usefulness for professional practice and it is the only tool which is significantly preferred to all other supports. CONCLUSION: In this study with students, the PDA is significantly more effective quantitatively and qualitatively than the tablet PC to retrieve drug information.
Attitude to Computers↗
Ophthalmologic and intraocular non-Hodgkin's lymphoma: a large single centre study of initial characteristics, natural history, and prognostic factors.
The aims of this study were to define the initial characteristics, natural history, and prognostic factors of patients with ophthalmologic and intraocular malignant lymphoma. All patients treated at the Institut Curie for lymphoma with ophthalmologic (orbit and/or adnexa) or intraocular involvement were retrospectively reviewed. A pathological review of all cases was performed according to the WHO classification. One hundred and forty-five patients were selected for the study. Pathological review showed 36% MALT type lymphoma, 22% lymphoplasmocytic lymphoma, and 15% diffuse large B-cell lymphoma. Ophthalmologic and ocular sites were intra-orbital in 61 cases (42%) and conjunctival in 51 cases (35%), with bilateral involvement in 10% of cases. Stage IV was found in 32% of cases, with bone marrow involvement in 12%. With a median follow-up of 90 months, the 5-year DFS and OS were 64 and 79% for low-grade NHL, and 43 and 50% for high-grade NHL. On multivariate analysis, age greater than 59 years, elevated LDH level, stage IV, high-grade histological subgroup, and presence of B-symptoms had a negative impact on OS for the overall population. In conclusion, with a median follow-up of 7.5 years, our large cohort of patients represents one of the largest published series on primary ophthalmologic and intraocular malignant lymphoma.
Adult↗
Second treatment with rituximab in B-cell non-Hodgkin's lymphoma: efficacy and toxicity on 41 patients treated at CHU-Lyon Sud.
The purpose of this study was to evaluate retrospectively the effect of a second treatment with rituximab for patients who progressed after a response to a first treatment. We analysed the charts of 41 patients treated at CHU Lyon-Sud between 1997 and May 2003. Patients were treated with rituximab alone or with a combination of rituximab and chemotherapy. The overall response rate (complete and partial response) was 73% for the second treatment. The median time to progression was longer but not significant for the second treatment in comparison with the first one (15.2 versus 11.3 months, P = 0.09). The second treatment was well tolerated. Thus, a second treatment with rituximab should be considered, alone or in combination with chemotherapy, for patients who progress after a first response to rituximab.
Adult↗
Short term Caco-2/TC7 cell culture: comparison between conventional 21-d and a commercially available 3-d system.
The Caco-2 cell model is a valuable tool for studying intestinal biotransformation of xenobiotics and to evaluate the potential of human intestinal absorption of new compounds. These properties were evaluated with Caco-2/TC7 cells in accelerated conditions to reduce maturation lag time from 21-d to 3-d in order to increase time and labor efficiency. Transmission electron and fluorescent microscopy were used for morphological characterization. Alkaline phosphatase and lactate dehydrogenase activities were assessed within time. Cytochrome P450 expression was studied by RT-PCR. Apparent permeabilities of a set of passively absorbed molecules across Caco-2/TC7 cell monolayers were determined to evaluate potential of both systems for prediction of human intestinal absorption. Microscopic images revealed that cells under both conditions differentiated as enterocyte-like cells but did so heterogeneously in the 3-d model. TEER values have shown that the 3-d model is a leakier cell system with higher mannitol Papp (cm/s). Biochemical characterization (hydrolase activities, CYP450 expression) suggested that the 3-d model was at a lower maturation level than the 21-d model. Carrier-mediated uptake of L-Phe was lower in the 3-d model suggesting that this model has limited application for mechanistic studies. Reasonable correlation was obtained between the two models (r2=0.88, p>0.01) for 11 passively absorbed compounds with high potential of rank ordering of compounds. Although results suggested that the 3-d cells are under-differentiated, they could be usable to estimate the oral absorption of passively absorbed compounds.
Biological Transport↗
Conserved methylation imprints in the human and mouse GRB10 genes with divergent allelic expression suggests differential reading of the same mark.
Grb10/GRB10 encodes a cytoplasmic adapter protein which modulates coupling of a number of cell surface receptor tyrosine kinases with specific signalling pathways. Mouse Grb10 is an imprinted gene with maternal-specific expression. In contrast, human GRB10 is expressed biallelically in most tissues, except for maternal-specific expression of one isoform in muscle and paternal expression in fetal brain. Owing to its location in 7p11.2-p12, GRB10 has been considered a candidate gene for the imprinted growth disorder, the Silver-Russell syndrome (SRS), but its predominantly biallelic expression argues against involvement in the syndrome. To investigate the discrepant imprinting between mouse and human, we compared the sequence organization of their upstream regions, and examined their allelic methylation patterns and the splice variant organization of the mouse locus. Contrary to expectation, we detected both maternal and paternal expression of mouse Grb10. Expression of the paternal allele arises from a different promoter region than the maternal and, as in human, is restricted to the brain. The upstream regions are well conserved, especially the presence of two CpG islands. Surprisingly, both genes have a similar imprinted methylation pattern, the second CpG island is a differentially methylated region (DMR) with maternal methylation in both species. Analysis of 24 SRS patients did not reveal methylation anomalies in the DMR. In the mouse this DMR is a gametic methylation mark. Our results suggest that the difference in imprinted expression in mouse and human is not due to acquisition of an imprint mark but in differences in the reading of this mark.
Animals↗