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Biomedical subjects

M Girard

Publications and source records attributed to M Girard.

At least 37 records · Page 2Linked to original sources
PubMed2001

Music decreases sedative requirements during spinal anesthesia.

UNLABELLED: Ambulatory surgery can create significant anxiety. This prospective study measured whether music can influence anxiety and perioperative sedative requirements in outpatients undergoing surgery with spinal anesthesia. We also evaluated the correlation between two anxiety measures, the State-Trait Anxiety Inventory test (STAI) and the 0- to 10-cm visual analog scale (VAS 0-10), with 0 meaning complete relaxation and 10 the worst feeling of anxiety possible. Fifty unpremedicated patients were randomly assigned to listen to music of their choice via headset during the perioperative period (Group I) or to have no music (Group II). All participants used patient-controlled IV midazolam sedation and underwent repeated evaluations of their anxiety level with the STAI and the VAS 0-10. Midazolam requirements during surgery (Group I, 0.6 +/- 0.7 versus Group II, 1.3 +/- 1.1 mg; P < 0.05) and for the whole perioperative period (Group I, 1.2 +/- 1.3 versus Group II, 2.5 +/- 2.0 mg; P < 0.05) were smaller in patients listening to music. Anxiety levels, measured with STAI or VAS 0-10, were similar in both groups. The Spearman's coefficient values between STAI and VAS 0-10 ranged from 0.532 to 0.687. We conclude that patients listening to music require less midazolam to achieve a similar degree of relaxation as controls and that measures of anxiety obtained from the STAI and the VAS 0-10 are positively, but only moderately, correlated. IMPLICATIONS: It is possible to decrease sedative requirements during surgery under spinal anesthesia by allowing patients to listen to music to reduce their anxiety.

Adult↗
PubMed2000

Processing, stability, and receptor binding properties of oligomeric envelope glycoprotein from a primary HIV-1 isolate.

The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) is thought to exist on the virion surface as a trimer of non-covalently associated gp120/gp41 molecules. We expressed trimeric envelope glycoprotein from three primary, macrophage tropic HIV-1 isolates in baby hamster kidney cells and analyzed the furin-mediated cleavage, stability, and receptor binding properties of the oligomers. The envelope glycoprotein was secreted in a soluble form deleted of its transmembrane anchor and the intracytoplasmic domain (gp140). A mixture of trimers, dimers, and monomers of gp140 as well as monomeric gp120 was detected on polyacrylamide gels. Analysis by sucrose gradient centrifugation revealed that trimers and dimers were essentially composed of uncleaved gp140, whereas most of the gp120 was found in the monomeric fraction. To analyze the effect of the cleavage of gp140 to gp120/Delta41 on trimerization, we co-expressed the furin protease along with gp140. Surprisingly, furin expression changed the subcellular localization of the envelope glycoprotein, which became in majority sequestered in the major furin compartment, the trans-Golgi network, as judged by confocal laser microscopy. The envelope glycoprotein secreted from furin-co-expressing cells was almost completely cleaved to gp120 and Deltagp41, but gp120 was found exclusively in the monomeric fraction, with a few residual oligomers being composed of uncleaved gp140. Secreted uncleaved gp140 trimers were purified to homogeneity and analyzed for their capacity to interact with cellular receptors CD4 and CC chemokine receptor 5 (CCR5). Receptor binding was analyzed on CD4- and CCR5-expressing cells as well as on peripheral blood mononuclear cells. Trimers showed greatly reduced binding to CD4 as compared with monomers. Neither monomers nor trimers bound directly to CCR5. In conclusion, our results show that the cleaved form of the envelope glycoprotein does not form stable trimers, suggesting that gp120/gp41 oligomers on the virion surface might be stabilized by a yet to be identified mechanism and that the virion might attach to CD4 via a monomeric form of gp120. These results are relevant to the development of an envelope-based vaccine against AIDS.

Animals↗
PubMed2000

Analysis of human parathyroid hormone (1-84) products. Separation of a major impurity in synthetic products by ion-pairing reversed-phase high-performance liquid chromatography.

Human parathyroid hormone (1-84) is a naturally occurring polypeptide that acts as the major regulator of calcium ion homeostasis. It can be efficiently produced through both synthetic and biosynthetic routes and, as such, highly selective analytical methods are required for the detection of a wide range of impurities. Herein we report on the development of an ion-pairing reversed-phase HPLC method for the analysis of human parathyroid hormone and the separation of impurities including a major, unidentified impurity detected in synthetic preparations. This impurity could not be resolved using trifluoroacetic acid-based methods generally used for monitoring purity levels in commercial products. Separation conditions consisted of a gradient elution of 0.155 M sodium chloride containing 0.037 M sodium pentanesulfonate, pH 5.6, as mobile phase A and acetonitrile as mobile phase B. Separations were carried out on an octadecylsilyl silica column maintained at 50 degrees C. Both column temperature and pH of mobile phase A significantly affected the separation of the major impurity. The major impurity eluted after the main human parathyroid peak and was detected in the two commercial synthetic products analyzed. Several minor impurities eluting before and after the main peak were also detected. Purity levels measured by the developed HPLC method (method C) were similar to those previously measured by capillary electrophoresis. Analysis of purified recombinant human parathyroid hormone did not show the presence of this impurity. This method offers a significant advantage for the purity assessment of human parathyroid hormone.

Chromatography, High Pressure Liquid↗
PubMed2000

Base-promoted in situ generation of methyl acrylate from dimethyl 3, 3'-dithiodipropionate. Application To N-alkylation of heterocycles

In basic medium, dimethyl 3,3'-dithiopropionate generates methyl acrylate, which serves in situ as a source of propionate moiety. This property was applied to the alkylation of indoles and other nitrogen heterocycles leading to a series of 3-(heteroaryl-substituted) propionates. A mechanistic rationale for the generation of acrylate is presented along with supportive experimental data.

Journal Article↗
PubMed2000

Generation of CD8+ T cell-generated suppressor factor and beta-chemokines by targeted iliac lymph node immunization in rhesus monkeys challenged with SHIV-89.6P by the rectal route.

The targeted lymph node (TLN) immunization strategy was investigated in macaques, in order to determine the efficacy in generating secretory, systemic, and cellular immune responses, CD8+ T cell-generated suppressor factors, and beta-chemokines. TLN immunization of the rectal and genital mucosa-associated iliac lymph nodes (TILNs) was compared with axillary TLN immunization (TAxLN) using HIV-1 MN/LAI gp140env and SIV p27gag in alum. Significantly higher immune responses, as well as CD8+ T cell-generated anti-SIV factors and the beta-chemokines RANTES, MIP-1alpha, and MIP-1beta, were elicited by iliac as compared with axillary TLN immunization. The immune responses induced by TLN immunization were examined for their capacity to prevent rectal mucosal infection by the pathogenic dual-tropic SHIV-89.6P. Despite significant secretory, serum, cellular, and beta-chemokine responses, the macaques were infected by SHIV-89.6P. Whether the lack of protection was associated with the antigenic unrelatedness of SHIV-89.6P to the immunizing HIV-1 MN/LAI gp140 or to the virus utilizing CXCR4 to a much greater extent than CCR5, remains to be determined.

Animals↗
PubMed2000

Monte Carlo calculation of the efficiency calibration curve and coincidence-summing corrections in low-level gamma-ray spectrometry using well-type HPGe detectors

Well-type high-purity germanium (HPGe) detectors are well suited to the analysis of small amounts of environmental samples, as they can combine both low background and high detection efficiency. A low-background well-type detector is installed in the Modane underground Laboratory. In the well geometry, coincidence-summing effects are high and make the construction of the full energy peak efficiency curve a difficult task with an usual calibration standard, especially in the high energy range. Using the GEANT code and taking into account a detailed description of the detector and the source, efficiency curves have been modelled for several filling heights of the vial. With a special routine taking into account the decay schemes of the radionuclides, corrections for coincidence-summing effects that occur when measuring samples containing 238U, 232Th or 134Cs have been computed. The results are found to be in good agreement with the experimental data. It is shown that triple coincidences effect on counting losses accounts for 7-15% of pair coincidences effect in the case of 604 and 796 keV lines of 134Cs.

Journal Article↗
PubMed2000

The choice of a diet quality indicator to evaluate the nutritional health of populations.

BACKGROUND: The USA and Canada both want to reduce social health inequalities in their population. These two countries have recently begun a process of harmonization of their nutrient recommendations. OBJECTIVE: To develop a standardized indicator to measure the impact of these recommendations on the health of different social groups in North America. The authors have compared three of the methods currently used for measuring overall diet quality for a population. DESIGN AND SETTING: The three methods, adjusted to the 1990 Canadian nutrition recommendations, were used to analyse the Québec Nutrition Survey data collected by Santé Québec in 1990. RESULTS: The authors found that the indicator developed by Kennedy and collaborators works best for analysing the Québec data. Moreover, it allows comparisons with the USA. Some questions, such as whether or not to add calories from alcohol consumption to the model and whether the indicators should be adjusted to the different cultures and specific population groups remain unanswered. CONCLUSIONS: In order to determine the role of nutrition in social health inequalities, it is important to develop standard indicators that are suitable for monitoring the relationship between dietary recommendations and eating habits.

Canada↗
PubMed2000

Cross-reactivity of anti-galactocerebroside autoantibodies with a Trypanosoma brucei proteolipidic epitope.

Pathogenic mechanisms of the demyelinating encephalopathy featuring the nervous phase of human African trypanosomiasis (HAT) are largely unknown. They might include autoimmune disorders. A variety of autoantibodies is detected during the disease and we have previously evidenced anti-galactocerebroside (GalC) antibodies in the serum and cerebrospinal fluid (CSF) from patients in the nervous stage (stage II) of HAT. We now show that anti-GalC antibodies recognize an antigen located on the parasite membrane and common to different strains of trypanosomes. By using affinity chromatography with a rabbit anti-GalC antiserum, a 52-kD proteolipid was isolated from the membrane of Trypanosoma brucei (T. b.) brucei AnTat 1.9, AnTat 1. 1E, and T. b. rhodesiense Etat 1.2/R and Etat 1.2/S. Antibodies directed against this antigen were found in the CSF from patients with nervous stage HAT. These CSF also contained anti-GalC antibodies and adsorption with the proteolipid decreased anti-GalC reactivity. Immunization of mice with this antigen induced the production of antibodies which cross-reacted with GalC but no protection from experimental infection with T. b. brucei. These data support the hypothesis that anti-GalC antibodies detected in the CSF from HAT patients might be induced by molecular mimicry with a parasite antigen.

Animals↗
PubMed2000

In vitro induction of nitric oxide synthase in astrocytes and microglia by Trypanosoma brucei brucei.

In stage II human african trypanosomiasis (HAT), which is characterized by central nervous system (CNS) involvement, neurones and oligodendrocytes might be targets of dysimmune processes. Nitric oxide (NO) production by peripheral macrophages is documented in HAT. We studied the production of NO by murine astrocytes and microglia cocultured with Trypanosoma brucei (T. b.) brucei AnTat 1.9. Purified astrocytes or microglia from mouse brains were cocultured with T. b. brucei, and in some instances with interferon (IFN)-gamma, which is known to be released during the disease and also to be a growth factor for trypanosomes. Inducible NO synthase (iNOS) expression was studied by indirect immunofluorescence and reverse transcriptase-polymerase chain reaction. NO production was determined by measuring nitrite generation in culture. Detection of iNOS in astrocytes and microglia in the presence of T. b. brucei, was closely associated with nitrite production and was strongly enhanced by the addition of IFN-gamma to the culture medium. The stimulation of iNOS activity required parasite-cell contact and likely occurred at the transcriptional level. This study demonstrates the induction of iNOS in CNS-related macrophage cells in the presence of trypanosomes and its potentiation by IFN-gamma.

Animals↗
PubMed2000

Testing the hypothesis of a recombinant origin of human immunodeficiency virus type 1 subtype E.

The human immunodeficiency virus type 1 (HIV-1) epidemic in Southeast Asia has been largely due to the emergence of clade E (HIV-1E). It has been suggested that HIV-1E is derived from a recombinant lineage of subtype A (HIV-1A) and subtype E, with multiple breakpoints along the E genome. We obtained complete genome sequences of clade E viruses from Thailand (93TH057 and 93TH065) and from the Central African Republic (90CF11697 and 90CF4071), increasing the total number of HIV-1E complete genome sequences available to seven. Phylogenetic analysis of complete genomes showed that subtypes A and E are themselves monophyletic, although together they also form a larger monophyletic group. The apparent phylogenetic incongruence at different regions of the genome that was previously taken as evidence of recombination is shown to be not statistically significant. Furthermore, simulations indicate that bootscanning and pairwise distance results, previously used as evidence for recombination, can be misleading, particularly when there are differences in substitution or evolutionary rates across the genomes of different subtypes. Taken jointly, our analyses suggest that there is inadequate support for the hypothesis that subtype E variants are derived from a recombinant lineage. In contrast, many other HIV strains claimed to have a recombinant origin, including viruses for which only a single parental strain was employed for analysis, do indeed satisfy the statistical criteria we propose. Thus, while intersubtype recombinant HIV strains are indeed circulating, the criteria for assigning a recombinant origin to viral structures should include statistical testing of alternative hypotheses to avoid inappropriate assignments that would obscure the true evolutionary properties of these viruses.

Evolution, Molecular↗
PubMed2000

[Survivorship of breast implants used in breast reconstruction. 949 implants].

The authors present from a series of 949 implants their method to calculate the life span of a mammary implant in the framework of breast reconstruction after cancer. In this statistical study, they have calculated the median life span of breast implants (loss of half of staff) by distinguishing it according to each type of implant (content, brand, indication...). The global median life span of a breast implant is 127 months. The median life span of a silicone gel-filled implant is superior than a saline implant because the frequency of deflation of saline implants is more important than the first one, despite that the real rupture percentage of silicone gel-filled implants is under-evaluated by the number of asymptomatic rupture. For saline implants, the median life span is clearly decreased by the initial under-inflation (108 months against 127 months) doubling the secondary deflation risk. In this series, the authors have been able to compare the evolution of implants according to their initial indication (reconstruction or aesthetic) and sometimes at a same patient, they have not observed significant difference of the median life span over a period of five years for an implant used in breast reconstruction after cancer or for an implant used in symmetricalization. In this series, the life span of saline implants is significant different in function of the brand of the implant demonstrating the comparative study usefulness by brands.

Adult↗
PubMed2000

[Macaque immunization with virions purified from a primary isolate of the human immunodeficiency virus type 1 induced enhancement antibodies].

Six Rhesus macaques were hyperimmunized with either live infectious human immunodeficiency virus type 1 (HIV-1) or with beta-propiolactone--or formalin--inactivated HIV-1. The virus used was HIV-1 BX08, a primary virus isolate grown in human PBMC. Instead of eliciting virus-neutralizing antibodies, this regimen induced antibodies that enhanced HIV-1 infectivity for PBMC by 10 to 90 fold. Enhancement was also seen in a cell-to-cell fusion assay using a Semliki Forest virus replicon to express BX08 gp160 in CD4+, CCR5+ HeLa cell cultures. These observations raise the concern that whole virus particles-based HIV-1 vaccines might elicit enhancing antibodies that could play a facilitating role in the transmission and/or evolution of the disease.

Animals↗
PubMed2000

[Sem: a suitable statistical software adaptated for research in oncology].

Many softwares have been adapted for medical use; they rarely enable conveniently both data management and statistics. A recent cooperative work ended up in a new software, Sem (Statistics Epidemiology Medicine), which allows data management of trials and, as well, statistical treatments on them. Very convenient, it can be used by non professional in statistics (biologists, doctors, researchers, data managers), since usually (excepted with multivariate models), the software performs by itself the most adequate test, after what complementary tests can be requested if needed. Sem data base manager (DBM) is not compatible with usual DBM: this constitutes a first protection against loss of privacy. Other shields (passwords, cryptage...) strengthen data security, all the more necessary today since Sem can be run on computers nets. Data organization enables multiplicity: forms can be duplicated by patient. Dates are treated in a special but transparent manner (sorting, date and delay calculations...). Sem communicates with common desktop softwares, often with a simple copy/paste. So, statistics can be easily performed on data stored in external calculation sheets, and slides by pasting graphs with a single mouse click (survival curves...). Already used over fifty places in different hospitals for daily work, this product, combining data management and statistics, appears to be a convenient and innovative solution.

Clinical Trials as Topic↗
PubMed2000

DNA vaccine protection against challenge with simian/human immunodeficiency virus 89.6 in rhesus macaques.

Twelve Rhesus macaques were immunized by intramuscular injection of naked DNA encoding the SlVmac gag and nef genes, HIV-1 89.6 env and rev genes and the simian interleukin-12 (IL-12) gene. Six of the animals also received two intramuscular injections of gp140 89.6 formulated in QS21. The monkeys were challenged by the intrarectal route, in parallel with six control monkeys, using 750 TCID50 of SHIV-89.6. Virus recovery in PBMC by co-cultivation was as follows: controls: six out of six; DNA only: five out of six; DNA + protein: two out of six. The five animals that remained virus free after this first challenge were challenged a second time, again by the intrarectal route and in parallel with four naive controls, using 600 TCID50 of pathogenic SHIV-89.6P. A rapid CD4 cell count decline was observed in the four control monkeys as well as in the monkey vaccinated with DNA only, but in none of the four animals immunized with DNA + protein. No virus was recovered from PBMC in two of these monkeys, and viral RNA loads in plasma were greatly reduced in three of them as compared with the controls. Absence of virus in PBMC was ascertained by whole blood transfusion to naive recipients. Altogether, this shows that the DNA prime-protein boost vaccine regimen could provide some protection against mucosal SHIV infection in rhesus monkeys, whereas DNA alone was ineffective.

AIDS Vaccines↗