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Biomedical subjects

P Girard

Publications and source records attributed to P Girard.

At least 19 recordsLinked to original sources
PubMed2001

The ep -->e'p eta reaction at and above the S11(1535) baryon resonance.

New cross sections for the reaction e p-->e p eta are reported for total center of mass energy W = 1.5--1.86 GeV and invariant momentum transfer Q2 = 0.25--1.5 (GeV/c)(2). This large kinematic range allows extraction of important new information about response functions, photocouplings, and eta N coupling strengths of baryon resonances. Newly observed structure at W approximately 1.65 GeV is shown to come from interference between S and P waves and can be interpreted with known resonances. Improved values are derived for the photon coupling amplitude for the S11(1535) resonance.

Journal Article↗
PubMed2001

Small-scale bioreactor system for process development and optimization.

An agitated 12-well microtiter plate system with a working volume of 2ml was investigated for cell culture process development. Agitation assures homogeneity in wells and enhances mass transfer between the gas and the liquid phase, thus improving maximum cell density and pH stability. The pH of the NaHCO(3)-buffered system can be adjusted by altering the carbon dioxide content of the gas phase. The non-toxic, visual pH indicator phenol red was used in combination with a spectrophotometric plate reader for rapid and precise pH measurements. For high throughputs, cell growth was assessed non-invasively using stable green fluorescent protein (GFP) expressing cells and a fluorescence plate reader. The setup is simple and inexpensive. The system can be automated and allows several hundred small-scale bioreactor experiments to be run in parallel.

Journal Article↗
PubMed2001

Feedback connections act on the early part of the responses in monkey visual cortex.

We previously showed that feedback connections from MT play a role in figure/ground segmentation. Figure/ground coding has been described at the V1 level in the late part of the neuronal responses to visual stimuli, and it has been suggested that these late modulations depend on feedback connections. In the present work we tested whether it actually takes time for this information to be fed back to lower order areas. We analyzed the extracellular responses of 169 V1, V2, and V3 neurons that we recorded in two anesthetized macaque monkeys. MT was inactivated by cooling. We studied the time course of the responses of the neurons that were significantly affected by the inactivation of MT to see whether the effects were delayed relative to the onset of the response. We first measured the time course of the feedback influences from MT on V1, V2, and V3 neurons tested with moving stimuli. For the large majority of the 51 neurons for which the response decreased, the effect was present from the beginning of the response. In the responses averaged after normalization, the decrease of response was significant in the first 10-ms bin of response. A similar result was found for six neurons for which the response significantly increased when MT was inactivated. We then looked at the time course of the responses to flashed stimuli (95 neurons). We observed 15 significant decreases of response and 14 significant increases. In both populations, the effects were significant within the first 10 ms of response. For some neurons with increased responses we even observed a shorter latency when MT was inactivated. We measured the latency of the response to the flashed stimuli. We found that even the earliest responding neurons were affected early by the feedback from MT. This was true for the response to flashed and to moving stimuli. These results show that feedback connections are recruited very early for the treatment of visual information. It further indicates that the presence or absence of feedback effects cannot be deduced from the time course of the response modulations.

Animals↗
PubMed2001

Response modulations by static texture surround in area V1 of the macaque monkey do not depend on feedback connections from V2.

We analyzed the extracellular responses of 70 V1 neurons (recorded in 3 anesthetized macaque monkeys) to a single oriented line segment (or bar) placed within the cell classical receptive field (RF), or center of the RF. These responses could be modulated when rings of bars were placed entirely outside, but around the RF (the "near" surround region), as described in previous studies. Suppression was the main effect. The response was enhanced for 12 neurons when orthogonal bars in the surround were presented instead of bars having the same orientation as the center bar. This orientation contrast property is possibly involved in the mediation of perceptual pop-out. The enhancement was delayed compared with the onset of the response by about 40 ms. We also observed a suppression originating specifically from the flanks of the surround. This "side-inhibition," significant for nine neurons, was delayed by about 20 ms. We tested whether these center/surround interactions in V1 depend on feedback connections from area V2. V2 was inactivated by GABA injections. We used devices made of six micropipettes to inactivate the convergent zone from V2 to V1. We could reliably inactivate a 2- to 4-mm-wide region of V2. Inactivation of V2 had no effect on the center/surround interactions of V1 neurons, even those that were delayed. Therefore the center/surround interactions of V1 neurons that might be involved in pop-out do not appear to depend on feedback connections from V2, at least in the anesthetized monkey. We conclude that these properties are probably shaped by long-range connections within V1 or depend on other feedback connections. The main effect of V2 inactivation was a decrease of the response to the single bar for about 10% of V1 neurons. The decrease was delayed by <20 ms after the response onset. Even the earliest neurons to respond could be affected by the feedback from V2. Together with the results on feedback connections from MT (previous paper), these findings show that feedback connections potentiate the responses to stimulation of the RF center and are recruited very early for the treatment of visual information.

Anesthesia↗
PubMed2001

Feedforward and feedback connections between areas V1 and V2 of the monkey have similar rapid conduction velocities.

It is often assumed that the action of cortical feedback connections is slow and modulatory, whereas feedforward connections carry a rapid drive to their target neurons. Recent results from our laboratory showed a very rapid effect of feedback connections on the visual responses of neurons in lower order areas. We wanted to determine whether such a rapid action is mediated by fast conducting axons. Using electrical stimulation, we compared the conduction velocities along feedforward and feedback axons between areas V1 and V2 of the macaque monkey. We conclude that feedback and feedforward connections between V1 and V2 have comparable fast conduction velocities (around 3.5 m/s).

Action Potentials↗
PubMed2000

[Detection of asymptomatic venous thrombosis after lower limb prosthetic surgery. Retrospective evaluation of a systematic approach using Doppler ultrasonography: 400 cases].

OBJECTIVES: The purpose of this study was to evaluate a pragmatic approach using duplex ultrasonography (US) for detecting deep vein thrombosis (DVT) after total hip (THA) and total knee (TKA) replacement. METHODS: Venous B-mode and color duplex US examination of both legs including a systematic evaluation of calf veins was performed twice during hospital stay (Between day 1 and day 4 for the first exam and between day 7 and day 11 for the second) in 400 consecutive patients. RESULTS: Deep vein thrombosis was diagnosed in 53 patients (13.5%) including 7 patients with proximal DVT. Thrombosis was asymptomatic in 46 patients (85%), and was bilateral or concerned the non-operated leg in 8 patients (14.5%). No clinical pulmonary embolism (PE) occurred during hospital stay (mean hospital stay: 12.3). Prior phlebitis and age over 70 were identified as a statistically significant risk-factor for post-operative DVT (p = 0.001 and p < 0.01 respectively) concerning the whole series and the THA series (p < 0.02 and p < 0.04 respectively). No statistically significant risk factor was founded for the TKA series (p < 0.2 and p < 0.2 respectively). All patients were seen at three months. Four patients (1.16%) developed DVT between hospital discharge and the 3-month follow-up visit. One patient with coronary disease died suddenly on post-operative day 24, without clinical signs or symptoms of PE or DVT. CONCLUSION: Venous US performed twice after total hip replacement detected asymptomatic DVT in 85% of patients. This approach might explain the absence of PE in our series and thus justify systematic ultrasonographic evaluation of lower limb veins after prosthetic replacement.

Adult↗
PubMed2000

Inter-study variability in population pharmacokinetic meta-analysis: when and how to estimate it?

Population pharmacokinetic analysis is being increasingly applied to individual data collected in different studies and pooled in a single database. However, individual pharmacokinetic parameters may change randomly from one study to another. In this article, we show by simulation that neglecting inter-study variability (ISV) does not introduce any bias for the fixed parameters or for the residual variability but may result in an overestimation of inter-individual (IIV) variability, depending on the magnitude of the ISV. Two random study-effect (RSE) estimation methods were investigated: (i) estimation, in a single step, of the three-nested random effects (inter-study, inter-individual and residual variability); (ii) estimation of residual variability and a mixture of ISV and IIV in the first step, then separation of ISV from IIV in the second. The one-stage RSE model performed well for population parameter assessment, whereas, the two-stage model yielded good estimates of IIV only with a rich sampling design. Finally, irrespective of the method used, ISV estimates were valid only when a large number of studies was pooled. The analysis of one real data set illustrated the use of an ISV model. It showed that the fixed parameter estimates were not modified, whether an RSE model was used or not, probably because of the homogeneity of the experimental designs of the studies, and suggest no study-effect in this example.

Computer Simulation↗
PubMed2000

A pharmacokinetic simulation model for ivabradine in healthy volunteers.

Ivabradine is a novel bradycardic agent that has been developed for the prevention of angina. Ivabradine has an active metabolite S-18982. The aim of this study is to develop a pharmacokinetic simulation model. Pharmacokinetic data from two studies were pooled and included data from a total of 66 healthy male volunteers. The data were collected following single dose intravenous and multiple dose oral administration of ivabradine. The multiple dose regimens were administered every 12 h and there were seven active dosing levels. The modelling was performed using the NONMEM software. The model was assessed in terms of its ability to describe the original data set used in its construction and also data arising from a different clinical pharmacology study involving 12 additional subjects. The pharmacokinetics of ivabradine and S-18982 were best described by two linked two compartment intravenous bolus and first-order input, with first-pass loss, and first-order output model. When the model was used for simulation it produced an adequate description of both the original data and data arising from a different clinical pharmacology study.

Benzazepines↗
PubMed2000

Population pharmacokinetics of doxorubicin, etoposide and ifosfamide in small cell lung cancer patients: results of a multicentre study.

AIMS: To determine the population pharmacokinetic (PK) parameters of doxorubicin (Dox), etoposide (Eto) and ifosfamide (Ifo) in small cell lung cancer (SCLC) patients, to assess the potential relationship between those parameters and to estimate the impact of individual morphological and biological covariates on patients' PK parameters. METHODS: Twenty-four patients with either SCLC limited to the thorax or extensive SCLC entered the study. All but one received at least two 3 day courses of the standard AVI (Dox 50 mg m-2 day 1, Eto 120 mg m-2 day 1,2,3, Ifo 2000 mg m-2 day 1,2) regimen. Individual blood samples were collected during each course and data on 47 courses were available. Data were analysed with the NONMEM program. Dox, Eto and Ifo plasma concentrations were studied with multicompartment (3, 2 and 2, respectively) models. Inter-individual and interoccasion (course-to-course) variabilities were estimated. The influence of individual covariates (age, sex, stage of the disease, weight, height, body-surface area, serum creatinine, total protein, LDH, ASAT, ALAT, alkaline phosphatase, gamma-GT, bilirubin) on PK parameters was also assessed. Correlations between individual PK parameters of Dox, Eto and Ifo were explored by using Pearson's correlation coefficient. RESULTS: Multiple data were available for each patient. Dox clearance (CL) and volume of distribution (Vd) were 32.0 l h-1 and 9.3 l (Inter-individual variability: 17.2% and 19.2%). Eto CL (l h-1) and Vd were, respectively, 3.34-0.0083* serum creatinine (micromol l-1) and 6.38 l (interindividual variability: 15.6% and 18.7%). Ifo CL and Vd at day 1 were 5.6 l h-1 and 26.0 l (interindividual variability: 10.1% and 17.2%, respectively). Estimation of course-to-course variability improved the precision of PK models in some cases. No correlation was observed between the respective PK parameters of each drug. Of individual covariates tested, only serum creatinine correlated with Eto CL (r = -0.37, P < 0.001). Self-induction of the metabolism of Ifo was apparent (mean CL increase from day 1 to day 2 : 42%) and individually correlated with the CL value at day 1 (r = -0.61, P < 0.001). CONCLUSIONS: Assessment of potential relationships between individual systemic exposure of chemotherapy and therapeutic endpoints (tumour response, toxicity and survival) will be required to adjust drugs dosages based on individual PK parameters rather than questionable body-surface area. However, all three drugs in the AVI regimen should be monitored simultaneously.

Aged↗
PubMed2000

Inferior vena cava interruption: how and when?

Interruption of the inferior vena cava (IVC) to prevent pulmonary embolism arising from venous thrombi in the lower extremities has become widely used since IVC filters became available about 30 years ago. However, reliable data regarding efficacy and safety of IVC filters are still lacking. The first controlled clinical trial of IVC filters demonstrated their effectiveness, but filters had no detectable impact on mortality and were associated with an increased risk of recurrent deep venous thrombosis. On the basis of the literature, indications for IVC interruption can be classified as accepted, debated, and debatable. The relevance of debated indications, more accurate identification of patients who remain "very high-risk" despite preventive or curative anticoagulant treatment, and selection of the most appropriate filter should be looked at in prospective clinical studies.

Contraindications↗
PubMed1999

Influence of the antioxidant quercetin in vivo on the level of nitric oxide determined by electron paramagnetic resonance in rat brain during global ischemia and reperfusion.

We characterized the changes in nitric oxide (NO) levels in the brain during global forebrain ischemia and reperfusion and tested the ability of the natural flavonoid, quercetin, and a synthetic flavonoid, FB277, to increase the amount of available NO by elimination of the superoxide radicals produced during reperfusion. In Sprague-Dawley rats, we used a four-vessel occlusion model of forebrain ischemia (15 min) and reperfusion (30 min). Brain NO was measured on samples of cerebral cortex and cerebellum ex vivo by electron paramagnetic resonance (EPR) spectroscopy. The spin trap used was diethyldithiocarbamate sodium salt (DETC) associated with ferrous citrate. The complex Fe(DETC)2NO was detected at 77 K as a triplet signal at g = 2.035. Groups of animals were treated with quercetin or FB277 (3-morpholinomethyl-3',4',5,7tetramethoxyflavone) or polyethylene glycol-conjugated superoxide dismutase (PEG-SOD). In control (intact anesthetized animals), the signal was about 3 times greater in the cortex than in the cerebellum. During ischemia, the signal rose to 110% in cortex (NS) and 283% in cerebellum (P < 0.05). In reperfusion, it fell again to 91% of control in cerebellum (NS) and 35% in cortex (P < 0.05). Treatment by quercetin (5 mg/kg i.v.) of intact and ischemia-reperfusion groups did not significantly change the signal amplitude in the cerebellum, but did double it in the cortex (to 76% of control) for the ischemia-reperfusion group (P < 0.05). In contrast, FB277 (3.75 mg/kg i.v.) did not increase the signal in the cortex during ischemia-reperfusion, but did do so in the cerebellum (to 152% of control, P < 0.05). The results obtained for PEG-SOD (10,000 U/kg i.v.) were similar to those for FB277. In separate in vitro measurements, we found that quercetin but not FB277 efficiently scavenged superoxide. We hypothesize that quercetin but not FB277 scavenged superoxide anions released in the cortex during reperfusion, thus diminishing the amount of NO removed by the formation of peroxynitrite. The lack of effect of PEG-SOD may be related to the need for chronic treatment to obtain protection.

Animals↗
PubMed1999

Chernobyl post-accident management: the ETHOS project.

ETHOS is a pilot research project supported by the radiation protection research program of the European Commission (DG XII). The project provides an alternative approach to the rehabilitation of living conditions in the contaminated territories of the CIS in the post-accident context of Chernobyl. Initiated at the beginning of 1996, this 3-y project is currently being implemented in the Republic of Belarus. The ETHOS project involves an interdisciplinary team of European researchers from the following institutions: the Centre d'etude sur l'Evaluation de la Protection dans le domaine Nucleaire CEPN (radiological protection, economics), the Institute National d'Agronomie de Paris-Grignon INAPG (agronomy, nature & life management), the Compiegne University of Technology (technological and industrial safety, social trust), and the Mutadis Research Group (sociology, social risk management), which is in charge of the scientific co-ordination of the project. The Belarussian partners in the ETHOS project include the Ministry of Emergencies of Belarus as well as the various local authorities involved with the implementation site. The ETHOS project relies on a strong involvement of the local population in the rehabilitation process. Its main goal is to create conditions for the inhabitants of the contaminated territories to reconstruct their overall quality of life. This reconstruction deals with all the day-to-day aspects that have been affected or threatened by the contamination. The project aims at creating a dynamic process whereby acceptable living conditions can be rebuilt. Radiological security is developed in the ETHOS project as part of a general improvement in the quality of life. The approach does not dissociate the social and the technical dimensions of post-accident management. This is so as to avoid radiological risk assessment and management being reduced purely to a problem for scientific experts, from which local people are excluded, and to take into consideration the problems of acceptability of decisions and the distrust of the population towards experts. These cannot be solved merely by a better communication strategy. This paper presents the main features of the methodological approach of the ETHOS project. It also explains how it is being implemented in the village of Olmany in the district of Stolyn (Brest region) in Belarus since March 1996, as well as its initial achievements.

Animals↗
PubMed1999

Cross-correlation study of the temporal interactions between areas V1 and V2 of the macaque monkey.

Cross-correlation studies performed in cat visual cortex have shown that neurons in different cortical areas of the same hemisphere or in corresponding areas of opposite hemispheres tend to synchronize their activities. The presence of synchronization may be related to the parallel organization of the cat visual system, in which different cortical areas can be activated in parallel from the lateral geniculate nucleus. We wanted to determine whether interareal synchronization of firing can also be observed in the monkey, in which cortical areas are thought to be organized in a hierarchy spanning different levels. Cross-correlation histograms (CCHs) were calculated from pairs of single or pairs of multiunit activities simultaneously recorded in areas V1 and V2 of paralyzed and anesthetized macaque monkeys. Moving bars and flashed bars were used as stimuli. The shift predictor was calculated and subtracted from the raw CCH to reveal interactions of neuronal origin in isolation. Significant CCH peaks, indicating interactions of neuronal origin, were obtained in 11% of the dual single-unit recordings and 46% of the dual multiunit recordings with moving bars. The incidence of nonflat CCHs with flashed bars was 29 and 78%, respectively. For the pairs of recording sites where both flashed and moving stimuli were used, the incidences of significant CCHs were very similar. Three types of peaks were distinguished on the basis of their width at half-height: T (<16 ms), C (between 16 and 180 ms), and H peaks (>180 ms). T peaks were very rarely observed (<1% in single-unit recordings). H peaks were observed in 7-16% of the single-unit CCHs, and C peaks in 6-16%, depending on the stimulus used. C and H peaks were observed more often when the receptive fields were overlapping or distant by <2 degrees. To test for the presence of synchronization between neurons in areas V1 and V2, we measured the position of the CCH peak with respect to the origin of the time axis of the CCH. Only in the case of a few T peaks did we find displaced peaks, indicating a possible drive of the V2 neuron by the simultaneously recorded V1 cell. All the other peaks were either centered on the origin or overlapped the origin of time with their upper halves. Thus similarly to what has been reported for the cat, neurons belonging to different cortical areas in the monkey tend to synchronize the time of emission of their action potentials with three different levels of temporal precision. For peaks calculated from flashed stimuli, we compared the peak position with the difference between latencies of V1 and V2 neurons. There was a clear correlation for single-unit pairs in the case of C peaks. Thus the position of a C peak on the time axis appears to reflect the order of visual activation of the correlated neurons. The coupling strength for H peaks was smaller during visual drive compared with spontaneous activity. On the contrary, C peaks were seen more often and were stronger during visual stimulation than during spontaneous activity. This suggests that C-type synchronization is associated with the processing of visual information. The origin of synchronized activity in a serially organized system is discussed.

Animals↗
PubMed1999

Clinical evaluation of the modified Brostrom-Evans procedure to restore ankle stability.

The modified Brostrom procedure has become the standard for anatomic repair of symptomatic chronic lateral instability. However, it was our perception that this local tissue repair may fail eventually, particularly in patients that are overweight, hyperflexible, or are involved in strenuous work or athletic activity. This is a retrospective review of 21 lateral ankle reconstructions (20 patients) in which the modified Brostrom technique was augmented with a portion of the peroneus brevis tendon. All patients were interviewed at an average of 29.5 months (range, 14-56 months postsurgery). Fourteen patients also agreed to be evaluated by a physical therapist. No surgical complications were identified. American Orthopaedic Foot and Ankle Society ankle-hindfoot scores averaged 98.2. There was no significant difference in passive or active range of motion of plantarflexion or dorsiflexion when compared to the contralateral ankle. However, a statistically significant loss of inversion (passive, P = 0.011; active, P = 0.018) and eversion (passive, P = 0.004; active, P = 0.007) was noted when compared to the contralateral ankle. Measurement of isometric eversion strength, using a Cybex 340 Isokinetic device, and functional testing, using a lateral lunge test, revealed no significant loss of peroneal strength. The authors conclude that chronic lateral ankle instability in the general population can be successfully managed with a modified Brostrom procedure augmented with a portion of the peroneus brevis. The procedure remains technically simple and provides a greater static restraint for inversion stress without evidence of dramatic overtightening or loss of peroneal strength.

Adult↗
PubMed1999

High prevalence of detectable deep venous thrombosis in patients with acute pulmonary embolism.

STUDY OBJECTIVES: Because specific studies are unavailable, the exact prevalence of detectable "residual" deep venous thrombosis (DVT) in patients with acute pulmonary embolism (PE) is unknown. DESIGN: Review of clinical records and radiologic documents of consecutive patients. SETTING: Pulmonary diseases and radiology departments at a university hospital. PATIENTS: All patients hospitalized in the Department of Pulmonary Diseases with a diagnosis of acute PE during a 5-year period (1984 to 1988). During this period, the diagnosis of PE was based exclusively on pulmonary angiography, and bilateral lower limb venography was routine in patients with proven acute PE. MEASUREMENTS AND RESULTS: Among 228 consecutive patients with angiography-proven PE, 213 underwent bilateral lower limb venography within 48 h of the diagnosis. Venography demonstrated DVT in 174 patients (81.7%; 95% confidence interval, 76.5 to 86.9%), including 128 patients (60%) with proximal DVT. Signs or symptoms of DVT were present in only 72 patients (42%) with DVT. The prevalence of detectable DVT was significantly lower in patients with recent pelvic surgery or delivery (6 of 12, 50%) than in the other patients, whatever their individual risk factors (p < 0.05). The mean pulmonary vascular obstruction was significantly lower in patients with normal venography than in patients with detectable DVT (37.6 +/- 20.9% vs 48.4 +/- 21.7%; p = 0.007). CONCLUSIONS: Lower limb venography demonstrates a high prevalence (82%) of residual DVT in patients with angiography-proven PE. These data should be taken into account in the diagnostic and therapeutic management of patients with suspected or proven PE.

Adolescent↗