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1.
Rev Sci Instrum ; 95(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38900095

ABSTRACT

Second generation quantum technologies aim to outperform classical alternatives by utilizing engineered quantum systems. Maintaining the coherence required to enable any quantum advantage requires detailed knowledge and control over the noise that the hosting system is subjected to. Characterizing noise processes via their power spectral density is routinely done throughout science and technology and can be a demanding task. Determining the phase noise power spectrum in leading quantum technology platforms, for example, can be either outside the reach of many phase noise analyzers or prohibitively expensive. In this work, we present and characterize a low-complexity, low-cost optical phase noise analyzer based on the short-delay optical self-heterodyne measurements for quantum technology applications. Using this setup, we compare two ≈1 Hz linewidth ultra-stable oscillators near 729 nm. Their measurements are used as a baseline to determine and discuss the noise floor achieved in this measurement apparatus with a focus on limitations and their tradeoffs. The achieved noise floor in this all-stock-component implementation of an optical phase noise analyzer compares favorably with commercial offerings. This setup can be used particularly without a more stable reference or operational quantum system as a sensor as would be the case for many component manufacturers.

2.
J Cyst Fibros ; 15(6): 825-833, 2016 11.
Article in English | MEDLINE | ID: mdl-27289197

ABSTRACT

BACKGROUND: Body composition (BC) analysis based on bioelectrical impedance analysis (BIA) provides conflicting results. The purpose of the study was to validate an equation specific for young patients with cystic fibrosis (CF), describe their BC and investigate its association with lung function. METHODS: Fifty-four young CF patients were evaluated by BIA and dual X-ray absorptiometry (DXA). An empirically derived CF-specific equation for fat-free mass (FFM) estimation by BIA was elaborated after stepwise multivariate regression and the agreement between BIA and DXA was assessed by Bland-Altman plots. The association between BC and lung function was investigated by regression analysis. RESULTS: The mean difference between the BIA and DXA assessment was close to zero. A total of 22.5% of patients (n=9) presented a FFM z-score≤-2. They had a worse pulmonary function and diaphragmatic impairment. Among these 9 patients, 7 had a normal BMI z-score>-1. CONCLUSIONS: BIA, based on a CF-specific equation, is a reliable method for BC assessment and allows the identification of patients at risk of nutritional degradation and bad respiratory prognosis.


Subject(s)
Body Composition , Cystic Fibrosis , Absorptiometry, Photon/methods , Adolescent , Body Mass Index , Child , Cystic Fibrosis/diagnosis , Cystic Fibrosis/physiopathology , Electric Impedance , Female , France , Humans , Male , Prognosis , Prospective Studies , Respiratory Function Tests/methods , Statistics as Topic , Young Adult
3.
Opt Express ; 22(19): 22632-48, 2014 Sep 22.
Article in English | MEDLINE | ID: mdl-25321732

ABSTRACT

We perform full 3D topology optimization (in which "every voxel" of the unit cell is a degree of freedom) of photonic-crystal structures in order to find optimal omnidirectional band gaps for various symmetry groups, including fcc (including diamond), bcc, and simple-cubic lattices. Even without imposing the constraints of any fabrication process, the resulting optimal gaps are only slightly larger than previous hand designs, suggesting that current photonic crystals are nearly optimal in this respect. However, optimization can discover new structures, e.g. a new fcc structure with the same symmetry but slightly larger gap than the well known inverse opal, which may offer new degrees of freedom to future fabrication technologies. Furthermore, our band-gap optimization is an illustration of a computational approach to 3D dispersion engineering which is applicable to many other problems in optics, based on a novel semidefinite-program formulation for nonconvex eigenvalue optimization combined with other techniques such as a simple approach to impose symmetry constraints. We also demonstrate a technique for robust topology optimization, in which some uncertainty is included in each voxel and we optimize the worst-case gap, and we show that the resulting band gaps have increased robustness to systematic fabrication errors.


Subject(s)
Computer Simulation , Models, Theoretical , Optics and Photonics , Photons , Refractometry/instrumentation , Crystallization , Equipment Design
4.
J Hosp Infect ; 84(1): 38-43, 2013 May.
Article in English | MEDLINE | ID: mdl-23433868

ABSTRACT

BACKGROUND: In Europe, including France, a measles outbreak has been ongoing since 2008. Unprotected healthcare workers (HCWs) may contract and spread the infection to patients. AIM: The objective of this study was to evaluate HCWs' measles immunity and vaccine acceptance in our setting. METHODS: In a survey-based study conducted in three university hospitals in Paris, 351 HCWs were included between April and June 2011. The following data were collected at enrolment: age, hospital unit, occupation, history of measles infection and vaccination, previous measles serology and acceptance of a measles vaccination in case of seronegativity. Sera were tested for the presence of specific anti-measles IgG antibodies using the CAPTIA(®) measles enzyme-linked immunosorbent assay. FINDINGS: The mean age of the participating HCWs was 36 years (range: 18-67) and 278 (79.2%) were female. In all, 104 four persons (29.6%) declared a history of measles, and 90 (25.6%) declared never having received a measles vaccination. Among the 351 HCWs included in the study, 322 (91.7%) were immunized against measles (IgG >90 mIU/mL). The risk factors for not being protected were age [18-29 years, adjusted odds ratio: 2.7 (95% confidence interval: 1.1-6.9) compared with ≥30 years], no history of measles infection or vaccination. The global acceptance rate for a measles vaccination, before knowing their results, was 78.6%. CONCLUSION: In this cohort of HCWs, 8.3% were susceptible to measles; the group most represented were aged <30 years. Acceptance of the measles vaccine was high. A vaccination campaign in healthcare settings should target specifically healthcare students and junior HCWs.


Subject(s)
Disease Outbreaks/prevention & control , Health Personnel/statistics & numerical data , Measles Vaccine/administration & dosage , Measles/prevention & control , Patient Acceptance of Health Care/statistics & numerical data , Vaccination/statistics & numerical data , Adolescent , Adult , Antibodies, Viral/blood , Enzyme-Linked Immunosorbent Assay , Female , Hospitals/standards , Humans , Immunity , Immunoglobulin G/blood , Logistic Models , Male , Measles/epidemiology , Paris/epidemiology , Surveys and Questionnaires , Young Adult
5.
J Hosp Infect ; 81(3): 169-76, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22627068

ABSTRACT

BACKGROUND: Two detailed checklists were developed, based on published infection control guidelines, for daily use by infection control practitioners in departments and operating rooms. AIM: To assess the impact of the checklists on nosocomial infection rates in three hospitals over the course of one year. METHODS: The checklists included 20 subheadings (± 150 items). Project nurses conducted rounds in the study (but not control) departments; during each round, the nurses selected 15-20 items for observation, marked the checklists according to appropriateness of observed behaviour and provided on-the-spot corrective education. Rates of adherence to the checklist, antibiotic use, number of obtained and positive cultures, and positive staff hand and patient environment cultures were reported monthly as a report card to relevant personnel and administrators. The rate of nosocomial infections was determined in the first and last months. RESULTS: The baseline nosocomial infection rate was similar in the study and control departments: 37/345 (11%) and 26/270 (10%) respectively. In the last month, the rate in the study department decreased to 16/383 (4%) (P<0.01); in the control it decreased insignificantly to 21/248 (8%) (not significant). No significant trends were detected in the number of obtained cultures, positive cultures, or antibiotic use. Adherence to guidelines ranged from 75% to 94% between the hospitals (P<0.001): the overall rate increased from 80% to 91% (P<0.01). CONCLUSIONS: The use of checklists during the conduct of infection control rounds, combined with monthly reports, was associated with a significant decrease in nosocomial infections in study departments.


Subject(s)
Checklist/statistics & numerical data , Cross Infection/prevention & control , Guideline Adherence , Infection Control/standards , Cross Infection/epidemiology , Cross Infection/microbiology , Gram-Negative Bacteria/classification , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/classification , Gram-Positive Bacteria/isolation & purification , Hand Disinfection/standards , Hospitals/standards , Humans , Infection Control/methods , Infection Control Practitioners
6.
Opt Express ; 20(4): 3877-82, 2012 Feb 13.
Article in English | MEDLINE | ID: mdl-22418144

ABSTRACT

We performed long-haul WDM transmission experiments to compare 10 Gbit/s MSK and QPSK modulation with a channel grid of 12.5 GHz. A standard link setup with inline dispersion compensation was applied in combination with coherent detection and following offline signal processing. Both modulation formats showed nearly equal performance bridging about 4000 km at a BER of 10(-3).

7.
Phys Rev E Stat Nonlin Soft Matter Phys ; 83(4 Pt 2): 046703, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21599330

ABSTRACT

We present and use an algorithm based on convex conic optimization to design two-dimensional photonic crystals with large absolute band gaps. Among several illustrations we show that it is possible to design photonic crystals which exhibit multiple absolute band gaps for the combined transverse electric and magnetic modes. The optimized crystals show complicated patterns which are far different from existing photonic crystal designs. We employ subspace approximation and mesh adaptivity to enhance computational efficiency. For some examples involving two band gaps, we demonstrate the tradeoff frontier between two different absolute band gaps.

8.
Neuroscience ; 158(4): 1446-59, 2009 Feb 18.
Article in English | MEDLINE | ID: mdl-19041929

ABSTRACT

Recent evidence demonstrates that N-methyl-d-aspartate receptor (NMDAR) trafficking contributes to synaptic plasticity in the hippocampus. Phosphorylation of tyrosine residues, especially NR2B tyrosine 1472, appears to be a mechanism by which NMDAR endocytosis is prevented, suggesting that the tyrosine phosphorylation and surface expression of NMDARs are positively correlated. Previous work from our laboratory and others has confirmed that modulation of tyrosine phosphatase and kinase activity alters the surface expression of NMDARs. However, the changes in NMDAR surface expression described in those studies were in terms of total surface membrane versus intracellular receptors. Within the plasma membrane of glutamatergic synapses, distinct populations of NMDARs exist. Namely, receptors at the surface can be differentiated into synaptic and extrasynaptic pools based on their association with the post-synaptic density (PSD) and availability to glutamate. In the present study, we utilized a subcellular fractionation approach coupled with detergent extraction to prepare synaptic and extrasynaptic NMDARs from adult rat hippocampal slices. Using this method, we examined how tyrosine phosphatase and Src-family tyrosine kinase (SFK) inhibitors modulate the phosphorylation and localization of these different pools of NMDARs. We found that both synaptic and extrasynaptic NMDARs were modulated by tyrosine phosphatase and SFK inhibitors; however subunit- and residue-specific effects were observed. Specifically, phosphorylation of NR2B tyrosine 1472 was associated with enrichment of synaptic NMDARs, whereas phosphorylation of NR2B tyrosine 1336 was associated with enrichment of extrasynaptic NMDARs. Using electrophysiological methods, we also reveal that the biochemical modifications produced by these inhibitors were associated with corresponding changes in NMDAR function.


Subject(s)
Hippocampus/cytology , Neuronal Plasticity/physiology , Receptors, N-Methyl-D-Aspartate/metabolism , Synapses/physiology , Animals , Bicuculline/pharmacology , Biophysical Phenomena , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , GABA Antagonists/pharmacology , Glutamic Acid/metabolism , Immunoprecipitation/methods , In Vitro Techniques , Male , Neurons/drug effects , Neurons/metabolism , Organometallic Compounds/pharmacology , Patch-Clamp Techniques , Phenanthrolines/pharmacology , Phosphorylation/drug effects , Protein Subunits/metabolism , Protein Transport , Protein Tyrosine Phosphatases/antagonists & inhibitors , Quinoxalines/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Subcellular Fractions/metabolism , Subcellular Fractions/ultrastructure , Synapses/ultrastructure , Tyrosine/metabolism
9.
Med Mal Infect ; 38(3): 119-24, 2008 Mar.
Article in French | MEDLINE | ID: mdl-18065179

ABSTRACT

UNLABELLED: In November 2001, the National Health Ministry of Rwanda advocated a new therapeutic protocol replacing chloroquine by an amodiaquine+sulfadoxine-pyrimethamine combination for the treatment of uncomplicated malaria. OBJECTIVES: This study had for aim to assess the application of this new protocol in Kigali healthcare institutions. POPULATION AND METHODS: A knowledge, attitudes and practices study (KAP) was carried out between June and August 2003. A questionnaire was answered by 120 care providers working in 15 healthcare institutions selected randomly in health facilities treating uncomplicated malaria. Antimalarial treatments prescribed to 150 patients were also reviewed from consultation files and analyzed. RESULTS: After analysis, 63.3% prescriptions were in line with the national protocol. Factors associated to the nonobservance of the national protocol were: the carer's ignorance of any recommended treatment, his doubt of efficacy of recommended drugs, and his fear of adverse effects. CONCLUSIONS: The authors recommend informing the care providers about the national protocol. Findings also demonstrate the need to include care providers in any modifications of the national policy in terms of drug efficacy and potential adverse effects of the new strategy.


Subject(s)
Antimalarials/therapeutic use , Guideline Adherence/statistics & numerical data , Health Plan Implementation/statistics & numerical data , Health Policy , Malaria/drug therapy , National Health Programs , Nursing Staff/statistics & numerical data , Physicians/statistics & numerical data , Adult , Amodiaquine/administration & dosage , Amodiaquine/therapeutic use , Antimalarials/administration & dosage , Drug Prescriptions/statistics & numerical data , Drug Therapy, Combination , Female , Health Facilities/statistics & numerical data , Health Knowledge, Attitudes, Practice , Humans , Male , Practice Patterns, Physicians'/statistics & numerical data , Program Evaluation , Pyrimethamine/administration & dosage , Pyrimethamine/therapeutic use , Rwanda , Sampling Studies , Sulfadoxine/administration & dosage , Sulfadoxine/therapeutic use , Urban Health
10.
J Physiol ; 575(Pt 1): 145-59, 2006 Aug 15.
Article in English | MEDLINE | ID: mdl-16762999

ABSTRACT

This study was designed to examine the neuronal mechanisms of ethanol sensitivity by utilizing inbred short sleep (ISS) and inbred long sleep (ILS) mouse strains that display large differences in sensitivity to the behavioural effects of ethanol. Comparisons of whole-cell electrophysiological recordings from CA1 pyramidal neurons in hippocampal slices of ISS and ILS mice indicate that ethanol enhances GABAA receptor-mediated inhibitory postsynaptic currents (GABAA IPSCs) and reduces NMDA receptor-mediated excitatory postsynaptic currents (NMDA EPSCs) in a concentration- and strain-dependent manner. In ILS neurons, these receptor systems are significantly more sensitive to ethanol than those in ISS neurons. To further examine the underlying mechanisms of differential ethanol sensitivities in these mice, GABAB activity and presynaptic and postsynaptic actions of ethanol were investigated. Inhibition of GABAB receptor function enhances ethanol-mediated potentiation of distal GABAA IPSCs in ILS but not ISS mice, and this blockade of GABAB receptor function has no effect on the action of ethanol on NMDA EPSCs in either mouse strain. Thus, subregional differences in GABAB activity may contribute to the differential ethanol sensitivity of ISS and ILS mice. Moreover, analysis of the effects of ethanol on paired-pulse stimulation, spontaneous IPSC events, and brief local GABA or glutamate application suggest that postsynaptic rather than presynaptic mechanisms underlie the differential ethanol sensitivity of these mice. Furthermore, these results provide essential information to focus better on appropriate target sites for more effective drug development for the treatment of alcohol abuse.


Subject(s)
Central Nervous System Depressants/pharmacology , Ethanol/pharmacology , Glutamic Acid/pharmacology , Hippocampus/drug effects , Synaptic Transmission , gamma-Aminobutyric Acid/pharmacology , Animals , Benzylamines/pharmacology , Dose-Response Relationship, Drug , Excitatory Postsynaptic Potentials , GABA Antagonists/pharmacology , Hippocampus/cytology , Hippocampus/metabolism , In Vitro Techniques , Male , Mice , Mice, Inbred Strains , N-Methylaspartate/pharmacology , Neurons/drug effects , Neurons/metabolism , Phosphinic Acids/pharmacology , Receptors, GABA-A/drug effects , Receptors, GABA-A/metabolism , Receptors, GABA-B/drug effects , Receptors, GABA-B/metabolism , Receptors, N-Methyl-D-Aspartate/drug effects , Receptors, N-Methyl-D-Aspartate/metabolism , Sleep/genetics
11.
Transplant Proc ; 37(1): 445-7, 2005.
Article in English | MEDLINE | ID: mdl-15808671

ABSTRACT

AIMS: Luminal administration of a preservation solution that prevents mucosal injury may decrease posttransplant complications. However, luminal administration of University of Wisconsin solution (UW) is controversial. In this study, we examined the potential of Celsior as a luminal small bowel preservation solution in comparison to UW or UW enriched with glutamine. METHODS: Small bowels of six normal WagRij rats were excised and divided into six equal segments. Each segment was luminally flushed with 10 mL ice-cold UW, UW with glutamine (20 g/L) or Celsior, and stored for 0, 2.5, and 24 hours at 4 degrees C. LDH, glucose, and lactate concentrations were determined in the preservation solutions. Histologic changes were determined using the Park score. RESULTS: Lactate dehydrogenase (LDH) was increased in all solutions after 2.5- and after 24-hour preservation. However, LDH was lower in Celsior than UW and UW with glutamine. Furthermore, higher glucose and lactate levels were found after 2.5- and 24-hour preservation in UW and UW with glutamine compared to Celsior. Histologically, jejunal segments were more susceptible to preservation than ileal segments, irrespective of the preservation solution used. Mucosal injury was evident after 2.5 hours (Park Scale 0-3) and increased significantly after 24 hours (park scale 3-6). CONCLUSIONS: Based on the lower glucose, lactate, and LDH levels in small intestines stored in Celsior, this study suggests that Celsior is a better luminal preservation solution than UW. Unfortunately, histological evaluations still show severe mucosal injury, indicating that there is a need for better luminal preservation solutions or for concomittant intravascular delivery of a preservation solution.


Subject(s)
Intestine, Small , Organ Preservation Solutions , Adenosine , Allopurinol , Animals , Disaccharides , Electrolytes , Glucose/analysis , Glutamates , Glutathione , Histidine , Insulin , L-Lactate Dehydrogenase/analysis , Lactic Acid/analysis , Male , Mannitol , Raffinose , Rats , Rats, Inbred Strains
12.
Brain Res ; 890(1): 86-99, 2001 Jan 26.
Article in English | MEDLINE | ID: mdl-11164771

ABSTRACT

Parkinson's disease (PD) is characterized by a degeneration of the dopamine (DA) pathway from the substantia nigra (SN) to the basal forebrain. Prior studies in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats have primarily concentrated on the implantation of fetal ventral mesencephalon (VM) into the striatum in attempts to restore DA function in the target. We implanted solid blocks of fetal VM or fetal striatal tissue into the SN to investigate whether intra-nigral grafts would restore motor function in unilaterally 6-OHDA-lesioned rats. Intra-nigral fetal striatal and VM grafts elicited a significant and long-lasting reduction in apomorphine-induced rotational behavior. Lesioned animals with ectopic grafts or sham surgery as well as animals that received intra-nigral grafts of fetal cerebellar cortex showed no recovery of motor symmetry. Subsequent immunohistochemical studies demonstrated that VM grafts, but not cerebellar grafted tissue expressed tyrosine hydroxylase (TH)-positive cell bodies and were associated with the innervation by TH-positive fibers into the lesioned SN as well as adjacent brain areas. Striatal grafts were also associated with the expression of TH-positive cell bodies and fibers extending into the lesioned SN and an induction of TH-immunolabeling in endogenous SN cell bodies. This finding suggests that trophic influences of transplanted fetal striatal tissue can stimulate the re-expression of dopaminergic phenotype in SN neurons following a 6-OHDA lesion. Our data support the hypothesis that a dopaminergic re-innervation of the SN and surrounding tissue by a single solid tissue graft is sufficient to improve motor asymmetry in unilateral 6-OHDA-lesioned rats.


Subject(s)
Brain Tissue Transplantation , Corpus Striatum/transplantation , Nerve Degeneration/surgery , Substantia Nigra/transplantation , Animals , Antiparkinson Agents/pharmacology , Apomorphine/pharmacology , Behavior, Animal/drug effects , Corpus Striatum/pathology , Male , Nerve Degeneration/chemically induced , Nerve Degeneration/pathology , Neurons/enzymology , Neurons/pathology , Oxidopamine , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/pathology , Parkinsonian Disorders/surgery , Rats , Rats, Inbred F344 , Recovery of Function , Substantia Nigra/pathology , Sympatholytics , Tyrosine 3-Monooxygenase/analysis
13.
Ann Surg ; 232(6): 804-13, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11088075

ABSTRACT

OBJECTIVE: To assess the effect on the function and immunologic status of potential donor livers of the duration of brain death combined with the presence and absence of hemodynamic instability in the donor. SUMMARY BACKGROUND DATA: Brain death, regarded as a given condition in organ transplantation, could have significant effects on the donor organ quality. METHODS: Brain death was induced in Wistar rats. Short or long periods of brain death in the presence or absence of hemodynamic instability were applied. Sham-operated rats served as controls. Organ function was studied by monitoring standard serum parameters. The inflammatory status of the liver was assessed by determining the immediate early gene products, the expression of cell adhesion molecules, and the influx of leukocytes in the liver. RESULTS: Progressive organ dysfunction was most pronounced in hemodynamically unstable brain-dead donors. Irrespective of hemodynamic status, a progressive inflammatory activation could be observed in brain-dead rats compared with controls. CONCLUSIONS: Brain death causes progressive liver dysfunction, which is made worse by the coexistence of hemodynamic instability. Further, brain death activates the inflammatory status of the potential donor liver, irrespective of the presence of hypotension. The changes observed may predispose the graft to additional damage from ischemia and reperfusion in the transplant procedure.


Subject(s)
Brain Death/physiopathology , Hemodynamics , Liver/physiopathology , Animals , Blood Chemical Analysis , Cell Adhesion Molecules/metabolism , Genes, Immediate-Early/genetics , Hypotension/physiopathology , Immunohistochemistry , Leukocytes/physiology , Liver/immunology , Liver/surgery , Liver Transplantation/physiology , Male , Rats , Rats, Wistar , Statistics, Nonparametric , Tissue Donors
14.
Orthopedics ; 23(8): 795, 799, 802, 804, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10952041

ABSTRACT

In situations where bone is lost secondary to trauma, the use of a hand-carved silicone block provides good results. When bone grafting is undertaken, a well-defined membrane will have enveloped the implant. Incising the membrane allows easy block removal, and after freshening the bone ends, a cavity awaits the bone graft. This technique offers simplicity and adequate stability for therapy, and secondary bone grafting is facilitated by the created space.


Subject(s)
Bone Resorption/etiology , Bone Resorption/surgery , Bone Transplantation/methods , Silicones , Wounds and Injuries/complications , Adolescent , Adult , Child , Debridement/methods , Female , Follow-Up Studies , Graft Survival , Humans , Male , Middle Aged , Prostheses and Implants
15.
Am J Obstet Gynecol ; 182(6): 1421-6, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10871458

ABSTRACT

OBJECTIVE: This study was undertaken to determine the feasibility of administering human menopausal gonadotropin subcutaneously for controlled ovarian hyperstimulation with intrauterine insemination. STUDY DESIGN: This was a prospective nonrandomized matched-group comparison. Study patients (n = 25) undergoing controlled ovarian hyperstimulation with intrauterine insemination infertility treatment between June 1998 and March 1999 self-administered human menopausal gonadotropin subcutaneously for ovulation induction. Cycles (n = 39) were analyzed for duration of human menopausal gonadotropin treatment, total number of ampules of human menopausal gonadotropin used, peak serum estradiol level, number of mature follicles (> or =15 mm), cycle fecundity, and acceptability of the subcutaneous route of human menopausal gonadotropin administration. Age-matched historical control subjects who followed the same protocol except for the route of human menopausal gonadotropin administration, which was instead intramuscular, were used for comparison. RESULTS: Study and control cycles did not differ with respect to duration of human menopausal gonadotropin treatment (7.49 vs 8.18 d), total number of ampules of human menopausal gonadotropin used (17.44 vs 19.55), peak serum estradiol level (881 vs 769 pg/mL), number of mature follicles (>/=15 mm; 3.39 vs 2.92), or cycle fecundity rate (15.4% vs 17.9%). Two study patients were switched from subcutaneous to intramuscular administration because of minor local injection site reactions. CONCLUSION: Subcutaneous human menopausal gonadotropin administration for controlled ovarian hyperstimulation with intrauterine insemination treatment cycles was generally well tolerated and yielded stimulation parameters and pregnancy rates similar to those associated with the intramuscular route. Patients subjectively preferred subcutaneous human menopausal gonadotropin administration because of the ability to self-administer the injections, the use of a smaller injection needle, and reduced muscular pain at the injection site.


Subject(s)
Fertility Agents, Female/therapeutic use , Menotropins/administration & dosage , Ovary/physiopathology , Adult , Estradiol/blood , Feasibility Studies , Female , Fertility , Humans , Injections, Intramuscular , Injections, Subcutaneous , Insemination, Artificial, Homologous , Menotropins/therapeutic use , Menstrual Cycle , Ovarian Follicle/physiopathology , Ovary/drug effects , Patient Satisfaction , Pregnancy Rate , Prospective Studies , Time Factors
16.
J Virol ; 73(9): 7882-5, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10438885

ABSTRACT

Polyomavirus middle T antigen does not overcome p53-mediated G(1) arrest in mouse embryo fibroblasts. Middle T antigen still associates with the signaling molecules phosphatidylinositol 3-kinase and SHC and activates the transcriptional activity of c-Myc and AP1 in p53-arrested cells. Examination of cell cycle regulatory proteins indicated that p53 does not interfere with these mitogenic signals but acts later in the G(1) phase of the cell cycle.


Subject(s)
Adaptor Proteins, Signal Transducing , Adaptor Proteins, Vesicular Transport , Antigens, Polyomavirus Transforming/metabolism , Mitogens/metabolism , Signal Transduction , Tumor Suppressor Protein p53/metabolism , Activating Transcription Factor 4 , Animals , Antigens, Polyomavirus Transforming/pharmacology , Cell Division , Cell Line , Cyclin-Dependent Kinase Inhibitor p21 , Cyclins/metabolism , Fibroblasts/cytology , Mice , Mitogens/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proteins/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Proto-Oncogene Proteins pp60(c-src)/metabolism , Shc Signaling Adaptor Proteins , Src Homology 2 Domain-Containing, Transforming Protein 1 , Trans-Activators/metabolism , Transcription Factor AP-1/metabolism
17.
J Exp Med ; 190(3): 399-410, 1999 Aug 02.
Article in English | MEDLINE | ID: mdl-10430628

ABSTRACT

The role of apoptosis in affinity maturation was investigated by determining the affinity of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific antibody-forming cells (AFCs) and serum antibody in transgenic mice that overexpress a suppressor of apoptosis, Bcl-xL, in the B cell compartment. Although transgenic animals briefly expressed higher numbers of splenic AFCs after immunization, the bcl-xL transgene did not increase the number or size of germinal centers (GCs), alter the levels of serum antibody, or change the frequency of NP-specific, long-lived AFCs. Nonetheless, the bcl-xL transgene product, in addition to endogenous Bcl-xL, reduced apoptosis in GC B cells and resulted in the expansion of B lymphocytes bearing VDJ rearrangements that are usually rare in primary anti-NP responses. Long-lived AFCs bearing these noncanonical rearrangements were frequent in the bone marrow and secreted immunoglobulin G(1) antibodies with low affinity for NP. The abundance of noncanonical cells lowered the average affinity of long-lived AFCs and serum antibody, demonstrating that Bcl-xL and apoptosis influence clonal selection/maintenance for affinity maturation.


Subject(s)
Antibody Affinity/genetics , Apoptosis/genetics , Apoptosis/immunology , Germinal Center/cytology , Germinal Center/immunology , Proto-Oncogene Proteins c-bcl-2/genetics , Animals , Antibodies/blood , Antibody Formation/genetics , Antibody-Producing Cells/cytology , Antibody-Producing Cells/immunology , Antibody-Producing Cells/metabolism , Antibody-Producing Cells/pathology , B-Lymphocyte Subsets/cytology , B-Lymphocyte Subsets/immunology , B-Lymphocyte Subsets/metabolism , B-Lymphocyte Subsets/pathology , Bone Marrow Cells/immunology , Bone Marrow Cells/pathology , Cell Differentiation/genetics , Cell Differentiation/immunology , Cell Survival/genetics , Cell Survival/immunology , Cells, Cultured , Gene Rearrangement, B-Lymphocyte, Heavy Chain/genetics , Immunoglobulin Variable Region/genetics , Lymphocyte Count , Mice , Mice, Inbred C57BL , Mice, Transgenic , Molecular Sequence Data , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Proto-Oncogene Proteins c-bcl-2/immunology , Spleen , Transgenes/immunology , bcl-X Protein
18.
Oncogene ; 18(1): 139-48, 1999 Jan 07.
Article in English | MEDLINE | ID: mdl-9926928

ABSTRACT

Retinoic acid inhibits transformation of cells by polyoma virus middle T oncoprotein. Inhibition of transformation results from a retinoic acid-dependent failure of cells to fully express the c-fos proto-oncogene. Retinoic acid prevents transactivation of the c-fos promoter by disrupting signaling between tyrosine kinases at the plasma membrane and trans-acting factors at the c-fos promoter. We used complementary genetic, biochemical and molecular approaches to demonstrate that: (1) phosphatidylinositol 3-kinase signaling is the principle mechanism of polyoma virus middle T oncoprotein activation of c-fos expression; (2) middle T/phosphatidylinositol 3-kinase transactivation of the c-fos promoter and transformation of cells requires activation of both the small GTP-binding protein Rac and Jun N-terminal kinase; (3) retinoic acid inhibits activation of Jun N-terminal kinase, thereby preventing c-fos transactivation and transformation; and (4) middle T activation of c-fos transcription requires both the serum response element and the promoter proximal cyclic AMP response element. These studies identify a novel target through which retinoids prevent oncogenic transformation.


Subject(s)
Antigens, Polyomavirus Transforming/metabolism , Cell Transformation, Neoplastic/drug effects , Mitogen-Activated Protein Kinases , Phosphatidylinositol 3-Kinases/metabolism , Promoter Regions, Genetic , Proto-Oncogene Proteins c-fos/genetics , Tretinoin/pharmacology , Antigens, Polyomavirus Transforming/genetics , Binding Sites , Calcium-Calmodulin-Dependent Protein Kinases/genetics , Calcium-Calmodulin-Dependent Protein Kinases/metabolism , GTP-Binding Proteins/genetics , GTP-Binding Proteins/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Humans , JNK Mitogen-Activated Protein Kinases , Proto-Oncogene Mas , Transcriptional Activation/drug effects , rac GTP-Binding Proteins
19.
J Pharmacol Exp Ther ; 288(1): 211-20, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9862773

ABSTRACT

We previously found that beta adrenergic agonists such as norepinephrine and isoproterenol potentiate the depressant actions of ethanol (EtOH) on cerebellar Purkinje neurons. Furthermore, antagonism of the beta adrenergic effects of endogenously released catecholamines with timolol reduced EtOH-induced depressions of neuronal activity in that brain area. In the present study, we further investigated the hypothesis that activity of the endogenous noradrenergic innervation to the cerebellar cortex can potentiate this EtOH action. We investigated the interaction of synaptically released catecholamines on EtOH-induced depressions of cerebellar Purkinje neurons in three different experiments: (1) endogenous catecholamine release was facilitated by applying the catecholamine uptake inhibitor desmethylimipramine, (2) activity of the noradrenergic innervation of the cerebellar cortex from locus ceruleus was increased by causing acute withdrawal from 7 days of chronic morphine treatment with the opiate antagonist naloxone, and (3) the noradrenergic innervation of the cerebellum was activated directly by electrical stimulation of the locus ceruleus. We found that all three conditions potentiated EtOH-induced depressions in the cerebellum and that this potentiation of ethanol effects could be antagonized by the systemic administration of the beta adrenergic antagonist propranolol. Furthermore, morphine withdrawal also caused potentiation of the depressant effects of phencyclidine, which are known to be regulated by the endogenous catecholamine innervation in this brain area. Taken together with our previous data demonstrating a beta adrenergic facilitation of EtOH actions in this brain area, the present results suggest that the activity of endogenous noradrenergic synapses can regulate the depressant effects of EtOH on cerebellar Purkinje neurons.


Subject(s)
Central Nervous System Depressants/pharmacology , Cerebellum/drug effects , Ethanol/pharmacology , Norepinephrine/metabolism , Adrenergic Uptake Inhibitors/pharmacology , Animals , Ataxia/chemically induced , Ataxia/metabolism , Ataxia/physiopathology , Cerebellum/metabolism , Cerebellum/physiopathology , Depression/chemically induced , Depression/metabolism , Depression/physiopathology , Desipramine/pharmacology , Drug Tolerance , Electric Stimulation , Locus Coeruleus/drug effects , Locus Coeruleus/physiopathology , Male , Naloxone/pharmacology , Narcotic Antagonists/pharmacology , Purkinje Cells/drug effects , Purkinje Cells/metabolism , Rats , Rats, Sprague-Dawley , Substance Withdrawal Syndrome/physiopathology
20.
Sante Publique ; 11(3): 253-69, 1999 Sep.
Article in French | MEDLINE | ID: mdl-10667053

ABSTRACT

A retrospective analysis of 211 consecutive complaints treated at the Direction of Health and Social Assistance of Paris was undertaken in order to specify the nature of the complaints and to evaluate their pertinence as an indicator of quality of care. The majority of complaints concern public and private health establishments, in particular surgery and psychiatric services. Although the study confirms the dysfunctioning of the organisation of services and also of therapeutic methods and medical treatments, the evaluation of iatrogenic risks and their avoidable nature is difficult and requires precise instruction. Complaints seem to be a neglected indicator of quality, yet they concern information that is accessible and could, if used with other information, be a first milestone in the vigilance of medical treatments.


Subject(s)
Patient Satisfaction , Psychiatric Department, Hospital/standards , Quality Indicators, Health Care , Sanitation/standards , Surgery Department, Hospital/standards , Humans , Iatrogenic Disease , Paris , Retrospective Studies , Sentinel Surveillance
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