Validation of Time-of-Voting-Decision Recall.
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Biomedical subjects
Publications and source records attributed to P Fournier.
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OBJECTIVE: The aim of this study was to assess the prognostic value of early brain scintigraphy in head injury in relation to long-term neuropsychological behavior. Twenty-four patients underwent technetium-99m (Tc-99m) ethyl cysteinate dimer single photon emission computed tomography (SPECT) within 1 month of the trauma. Scintigraphic abnormalities were evaluated both visually and semiquantitatively using the brain-to-cerebellum ratio method. The clinical neuropsychological investigation was conducted to evaluate abnormalities related to motor deficit, frontal behavior, and memory and language disorders. All patients had abnormalities on SPECT scan. One year after trauma, 14 patients (58%) had neuropsychological sequelae. The brain-to-cerebellum ratios in the left basal ganglia and brain stem were significantly decreased in patients with memory disorders (P = .03 and P = .02, respectively). Moreover, SPECT visual analysis indicated that low uptake in the basal ganglia, thalamus, and brain stem was associated with subsequent motor deficit, frontal behavior, and language and memory disorders. The authors conclude that brain SPECT can be valuable in predicting the neuropsychological behavior of survivors of severe head injury.
We report microwave cavity perturbation measurements of the temperature dependence of the penetration depth, lambda(T), and conductivity, sigma(T) of Pr(2-x)Ce(x)CuO(4-delta) (PCCO) crystals, as well as parallel-plate resonator measurements of lambda(T) in PCCO thin films. Penetration depth measurements are also presented for a Nd(2-x)Ce(x)CuO(4-delta) (NCCO) crystal. We find that Deltalambda(T) has a power-law behavior for T<T(c)/3, and conclude that the electron-doped cuprate superconductors have nodes in the superconducting gap. Furthermore, using the surface impedance, we have derived the real part of the conductivity, sigma(1)(T), below T(c) and found a behavior similar to that observed in hole-doped cuprates.
The in-plane magnetic penetration depth, lambda(T), was measured down to 0.4 K in single crystals of electron-doped superconductors, Pr(1.85)Ce(0.15)CuO(4-delta) (PCCO) and Nd(1.85)Ce(0.15)CuO(4-delta) (NCCO). In PCCO, the superfluid density varies as T2 from 0.025 up to roughly 0.3T/T(c) suggestive of a d-wave state with impurities. In NCCO, lambda(T) shows a pronounced upturn for T<4 K due to the paramagnetic contribution of Nd3+ ions. Fits to an s-wave order parameter over the standard BCS range (T/T(c) = 0.32) limit any gap to less than Delta(min)(0)/T(c) = 0.57 in NCCO. For PCCO, the absence of paramagnetism permits a lower temperature fit and yields an upper limit of Delta(min)(0)/T(c) = 0.2.
In good conductors optical phonons are usually screened, and therefore not observed. However, sharp features due to infrared-active modes in the copper-oxygen planes are observed in the optical conductivity of Pr1.85Ce0.15CuO4 and YBa2Cu3O6.95. Oscillator strengths indicate that the screening of these modes is poor or totally absent. These materials are compared with eta-Mo4O11, in which lattice modes appear suddenly below the charge-density wave transition. It is proposed that poor screening in the cuprates originates from fluctuating charge inhomogeneities in the copper-oxygen planes.
To optimize polynucleotide vaccinations for protective antitumor immunity we used a self-replicating RNA vaccine in which Semliki Forest virus replicase drives RNA expression of the lacZ gene coding for beta-galactosidase as model tumor-associated antigen (TAA). This was compared with replicase-deficient control RNA and with lacZ DNA plasmids with respect to gene expression in vitro and in vivo and for vaccination using the mouse ear pinna as an optimal immunization site. In vitro, the highest expression was observed with self-replicating RNA. Gene expression following pinna inoculation of either non-replicating DNA plasmids or self-replicating RNA was similar, lasting for 2-3 weeks. Higher antibody responses were obtained with RNA than with DNA. beta-Gal peptide specific CTL memory responses to lacZ DNA or RNA lasted for more than 6 weeks while respective responses induced by lacZ-transfected tumor cells lasted for only 2 weeks. To achieve a protective response against lacZ tumor cells with self-replicating RNA about a 100-fold lower dose of polynucleotide was sufficient in comparison to DNA. The extent of protective antitumor immunity not only depended on the gene dose used for vaccination, but also on the aggressiveness of the lacZ-transfected tumor line used for challenge. In comparison to lacZ-transfected tumor cells as vaccines, polynucleotide vaccination also demonstrated superiority with regard to cross-protection. Protective antitumor immunity could be strongly increased upon co-inoculation of lacZ DNA with IL-2 DNA or IL-12 RNA. IL-2 DNA, but not IL-12 RNA, also augmented the CTL response while IL-12 RNA, but not IL-2 DNA, reduced the antibody response. These results demonstrate efficient protective antitumor immunity after intra-pinna lacZ TAA polynucleotide vaccination and show additional immunomodulatory effects by co-administration of cytokine polynucleotides.
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Sf21 and Sf9 cell lines established from the lepidoptera Spodoptera frugiperda do not display major induction of heat shock proteins when exposed to a temperature of 37 degrees C. After some months of adaptation at 37 degrees C we obtained two new cell lines, Sf21-HT and Sf9-HT, which have now been established for several years in our laboratory. The Sf9-HT line displays a slightly shorter doubling time at 37 degrees C than the wild type at 28 degrees C, but cell lethality gives rise to an earlier growth arrest. The composition of total lipid extract from heat-adapted cells reveals a higher sphingomyelin to phosphatidylcholine ratio and a higher percentage of saturated fatty acids, which are expected for the lower membrane fluidity, required for thermotolerance. The cell volume of Sf9-HT is doubled, and by flow cytometry we showed that the DNA content is twice that in the parental cell line. Karyotypic examination of metaphasic cells achieved under epifluorescence microscopy revealed a doubled chromosome number in Sf9-HT.
Nine-banded (n = 47) and great (n = 31) long-nosed armadillos (Dasypus novemcinctus and Dasypus kappleri) were immobilized for clinical examination and collection of biological samples as part of a wildlife rescue during the filling of a hydroelectric dam (Petit Saut, French Guiana) from May 1994 to April 1995. Three intramuscular (i.m.) anesthetic combinations were evaluated: (1) tiletamine/zolazepam (T/Z) at a dose of 8.5 mg/kg in 12 nine-banded long-nosed armadillos (NBA) and 10 great long-nosed armadillos (GLA), (2) ketamine at 40 mg/kg combined with xylazine at 1.0 mg/kg (K/X) in 18 NBA and nine GLA, and (3) ketamine at 7.5 mg/kg combined with medetomidine at 75 microng/kg (K/M) in 17 NBA and 12 GLA, antagonized by 375 microg/kg atipamezole. Induction was smooth, ranged from mean +/- SD = 2.8+/-0.6 to 4.3+/-1.8 min, and did not differ significantly between protocols, species, or sex. In NBA, immobilization time ranged from 43.8+/-27.8 to 66.5+/-40.0 min and did not differ between protocols or sex. Muscle relaxation was judged to be better with K/X and K/M versus T/Z. In GLA, the response to the anesthetic protocols was more variable and immobilization time ranged from 30.4+/-6.2 to 98.4+/-33.7 min. The main difference was observed in GLA females receiving the T/Z combination, in which immobilization time was significantly longer versus males, but also versus GLA K/M group, and versus NBA T/Z group. Effects on body temperature, heart rate and respiratory rate were limited. Thirty six to 50% of the individuals showed hypoxemia (SpO2 < 85%) throughout anesthesia and values <80% also were recorded but the hypoxemia was not associated with clinical signs. With T/Z and K/X, recovery was irregular and prolonged up to 2 to 3 hr in some individuals. In K/M groups, first standing was observed 1.0 to 16.4 min after i.m. atipamezole injection without adverse effects. Finally, the three anesthetic combinations used in this study were effective and safe agents for 30 to 40 min immobilizations including minor surgery procedures. The ability to antagonize the medetomidine-induced sedation with atipamezole significantly reduces the recovery time, making the K/M combination preferable, especially in field conditions.
Even mild, head injury during pregnancy can threaten either the maternal or the fetal life. Traffic accidents are the main causes so head injury is often associated with other lesions, frequently abdominal trauma. Among all these possible lesions, head injury and hemorrhagic shock are the main sources of fatality in pregnant women. All kinds of trauma and especially head injuries have a potentially deleterious effect on fetal viability. This risk is associated with systemic and cerebral consequences of post-traumatic arterial hypotension, anoxia or anemia. Moreover, diagnostic procedures and medications can add their noxious secondary effects, contributing more or less to poor fetal outcome. Decision making is necessarily dictated by the severity of the consciousness disorders and/or the encephalic lesions. A convergent discussion between the intensive care physician, the neurosurgeon, the obstetrician and the anesthesiologist is needed. Severe or prolonged traumatic coma is highly dramatic situation because the maternal outcome remains largely unknown for days or weeks. Technically, for these severe comas, there are no substantial differences with what is usually done in a similar case without pregnancy. Neurosurgical indications follow the usual rules, except that some non-urgent indications should be delayed for a while. Usually, this simple rule of independency in indications also applies to the obstetrician. Special care must be taken for fetal monitoring required throughout the initial critical phase.
OBJECTIVE: This study aims to identify the determinants of compliance with the recommendation to visit a physician for advice which was given to individuals whose cholesterolemia was > 6.2 mmol/l at mass screening for risk factors of cardiovascular diseases. METHODS: Data were collected from 1144 adults found to be hypercholesterolemic during a screening programme in 54 work sites and 29 public areas and contacted by phone two to six months later. Based on the Health Belief Model, perceived seriousness, perceived self-efficacy, and cues to action were measured. Potential determinants of compliance to the recommendation were examined using multivariate analyses. RESULTS: Mean compliance was 58.6%. For the perceived seriousness dimension of the Health Belief Model, personal history of CVD or risk factors, and prior awareness of cholesterol levels were important determinants. Those already treated for hypercholesterolemia comply twice as much as those who were aware and untreated. Among cues to action, higher cholesterol levels and hypertension are associated with greater compliance; however, smokers were less likely to comply. The dimension of perceived self-efficacy, as measured by ease of access to health services and prior success in eating habit modification, is also associated with compliance to the recommendation. Compliance increases significantly with age. For those previously aware of their elevated cholesterol level, variables representing perceived self-efficacy were no longer determinants. For those previously unaware of their elevated cholesterol level, variables representing CVD perceived threat do not influence compliance. CONCLUSION: The Health Belief Model appears to be an appropriate framework to the determinants of compliance with the recommendation to visit a doctor during mass screening.
We have previously shown that both a centromere (CEN) and a replication origin are necessary for plasmid maintenance in the yeast Yarrowia lipolytica (). Because of this requirement, only a small number of centromere-proximal replication origins have been isolated from Yarrowia. We used a CEN-based plasmid to obtain noncentromeric origins, and several new fragments, some unique and some repetitive sequences, were isolated. Some of them were analyzed by two-dimensional gel electrophoresis and correspond to actual sites of initiation (ORI) on the chromosome. We observed that a 125-bp fragment is sufficient for a functional ORI on plasmid, and that chromosomal origins moved to ectopic sites on the chromosome continue to act as initiation sites. These Yarrowia origins share an 8-bp motif, which is not essential for origin function on plasmids. The Yarrowia origins do not display any obvious common structural features, like bent DNA or DNA unwinding elements, generally present at or near eukaryotic replication origins. Y. lipolytica origins thus share features of those in the unicellular Saccharomyces cerevisiae and in multicellular eukaryotes: they are discrete and short genetic elements without sequence similarity.
PURPOSE: Concurrent biochemotherapy results in high response rates but also significant toxicity in patients with metastatic melanoma. We attempted to improve its efficacy and decrease its toxicity by using decrescendo dosing of interleukin-2 (IL-2), posttreatment granulocyte colony-stimulating factor (G-CSF), and low-dose tamoxifen. PATIENTS AND METHODS: Forty-five patients with poor prognosis metastatic melanoma were treated at a community hospital inpatient oncology unit affiliated with the John Wayne Cancer Institute (Santa Monica, CA) between July 1995 and September 1997. A 5-day modified concurrent biochemotherapy regimen of dacarbazine, vinblastine, cisplatin, decrescendo IL-2, interferon alfa-2b, and tamoxifen was repeated at 21-day intervals. G-CSF was administered beginning on day 6 for 7 to 10 days. RESULTS: The overall response rate was 57% (95% confidence interval, 42% to 72%), the complete response rate was 23%, and the partial response rate was 34%. Complete remissions were achieved in an additional 11% of patients by surgical resection of residual disease after biochemotherapy. The median time to progression was 6.3 months and the median duration of survival was 11.4 months. At a maximum follow-up of 36 months (range, 10 to 36 months), 32% of patients are alive and 14% remain free of disease. Decrescendo IL-2 dosing and administration of G-CSF seemed to reduce toxicity, length of hospital stay, and readmission rates. No patient required intensive care unit monitoring, and there were no treatment-related deaths. CONCLUSION: The data from this study indicate that the modified concurrent biochemotherapy regimen reduces the toxicity of concurrent biochemotherapy with no apparent decrease in response rate in patients with poor prognosis metastatic melanoma.
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Wild red howler monkeys (Alouatta seniculus) were translocated during the flooding of the forest at a hydroelectric dam site in French Guiana. For a variety of minor clinical procedures, 96 monkeys were anesthetized with various intramuscular injections of combinations of medetomidine and ketamine. The howler population was composed of healthy animals (42 males and 54 females) of various ages. Medetomidine (150 micrograms/kg) associated with ketamine (4 mg/kg) gave the best results and was used on 63 animals. The injection rapidly resulted in complete immobilization with good to excellent myorelaxation. The induction stage was quiet, with absence of both corneal and pedal withdrawal reflexes in 57 animals after 2.9 +/- 1.4 min. Six animals required an additional injection. Rectal temperature and respiratory and heart rates decreased during anesthesia, whereas relative oxyhemoglobin saturation increased. One death occurred during anesthesia. One abortion and one death also occurred the day following anesthesia but were more probably a result of capture stress. Atipamezole given i.m. at a dose of five times the medetomidine dose 38.4 +/- 8.0 min after the anesthetic injection led to standing recovery in 7.1 +/- 4.5 min. Spontaneous recovery occurred in 17 animals before the atipamezole injection after an average of 30.6 +/- 9.6 min. Total recovery time was shorter in young animals. Medetomidine/ketamine induced good myorelaxation and provided considerably shortened immobilization duration, which are two notable advantages for field studies. We recommend this association for short procedures including minor surgery in red howler monkeys.
Antigenicity and conformational propensities of synthetic peptides corresponding to the sequential epitope H236-255 of the measles virus hemagglutinin protein were investigated. This epitope corresponds to the neutralising and protective monoclonal antibody BH129 and includes Arg243, implicated in CD46-down-regulation and Arg253 that has been mapped to the putative enzymatic site. Fine mapping with truncation-, elongation-, Gly- and Ala-substitution analogues defined EL-QL as the critical residues of the minimal epitope S244ELSQL249. CD spectra of peptides, comparison with the 3D-structure of homologous sequences, and prediction algorithms suggested a helical structure with the contact residues E245L-QL249 located on the protein surface. Mimotopes obtained with a 6-mer phage display library contained a consensus Pro (important for binding) instead of Ser247 of the wild-type sequence (irrelevant for binding). The kink induced by Pro seemed to be essential to bring the 4 contact-residues in the mimotopes and in the corresponding short peptides together. CD analysis and prediction algorithms suggested that non-helical conformations of the phage insert and of the peptides may favourably mimic the antigenic helical turns of the wild-type sequence, resulting in an up to 135 times higher antigenicity of the mAb towards the mimotope peptides.
Simplified tests based on recombinant antigens are considered to be important for monitoring immunity against measles virus (MV). The hemagglutinin protein (H) is the main target for neutralising and protective antibodies. We produced a recombinant MV-H protein, in a high-yield mammalian expression system based on the Semliki Forest virus replicon. The antigenicity of this recombinant protein was investigated with monoclonal antibodies and its suitability for measuring the immune status of vaccinees was tested in a large cohort by ELISA (H-ELISA). The results were evaluated against neutralisation (NT) and hemagglutination inhibition (HI) titers and MV-specific IgG measured in a commercial whole-virus based ELISA (MV-ELISA, Enzygnost). The H-ELISA correlated better with HI (r=0.78) and NT titers (r=0.80), than the MV-ELISA (HI, r=0.58; NT, r=0.59). In contrast to the MV-ELISA, the H-ELISA detected no false-positive sera (P < 0.02) and the number of false-negative sera was significantly lower in the H-ELISA than in the MV-ELISA (4/378 vs. 15/378; P < 0.025). The performance of the H-ELISA did not deteriorate significantly when, instead of background corrected net values, uncorrected raw O.D. values of the H-antigen were considered, or when early time points (30 min) were evaluated. These results demonstrate that the recombinant H-ELISA detects efficiently non-immune individuals among vaccinees, despite their relatively low MV-antibody levels. A simplified format with single value measurements did not result in loss of sensitivity or specificity and its performance compared favorably with commercial ELISAs based on whole virus.
The success of strategies to revitalize primary health care services such as those advocated by the Bamako Initiative requires a response adapted to the expectations of the population, especially in terms of quality. The goal of this study, conducted in two rural communities in Guinea, was to identify, characterize, and classify the criteria that the public uses to judge the quality of primary health care (PHC) services. This study included 180 participants in 21 focus group discussions. Forty-four main criteria were identified. These criteria vary depending on the respondents' sex and age, and their ability to access primary health care services. Some of the criteria correspond to those used by health care providers, while others do not. The general public places considerable emphasis on outcomes, but little emphasis on preventive services. The users appear very sensitive to aspects of the interpersonal relations they have with professionals and the technical quality of the care provided. A taxonomy of perceived quality is developed, which includes the following five categories: (1) technical competence of the health care personnel; (2) interpersonal relations between the patients and care providers; (3) availability and adequacy of resources and services; (4) accessibility and (5) effectiveness of care. It is a major challenge to refocus on quality in the development of health care services. This will require considerable changes for which training may be an effective, but certainly not a sufficient means. Promoting professionalism and changing the relations between public authorities and the general public are the only means of improving the quality of health care services as well as user perception.