Biomedical subjects

P Girard

Publications and source records attributed to P Girard.

At least 19 recordsLinked to original sources

PubMed2006

Auger electrons--a nanoprobe for structural, molecular and cellular processes.

This paper provides a brief review of recently published work on biophysical and biological aspects of Auger processes. Three specific questions have been considered. (1) Does charge neutralisation contribute to molecular damage such as DNA strand breaks? (2) How many DNA double strand breaks are produced by a single decay of DNA bound (125)I? (3) What is the correlation between number of gammaH2AX foci and number of double strand breaks (DSB)? The paper also gives preliminary reports on two new calculations: (a) calculation of the spectrum of Auger electrons released during decay of (124)I and (b) the use of Auger electrons in the decay of (125)I as a probing agent of novel DNA structures.

Computer Simulation↗

PubMed2006

Modelling response time profiles in the absence of drug concentrations: definition and performance evaluation of the K-PD model.

The plasma concentration-time profile of a drug is essential to explain the relationship between the administered dose and the kinetics of drug action. However, in some cases such as in pre-clinical pharmacology or phase-III clinical studies where it is not always possible to collect all the required PK information, this relationship can be difficult to establish. In these circumstances several authors have proposed simple models that can analyse and simulate the kinetics of the drug action in the absence of PK data. The present work further develops and evaluates the performance of such an approach. A virtual compartment representing the biophase in which the concentration is in equilibrium with the observed effect is used to extract the (pharmaco)kinetic component from the pharmacodynamic data alone. Parameters of this model are the elimination rate constant from the virtual compartment (KDE), which describes the equilibrium between the rate of dose administration and the observed effect, and the second parameter, named EDK(50) which is the apparent in vivo potency of the drug at steady state, analogous to the product of EC(50), the pharmacodynamic potency, and clearance, the PK "potency" at steady state. Using population simulation and subsequent (blinded) analysis to evaluate this approach, it is demonstrated that the proposed model usually performs well and can be used for predictive simulations in drug development. However, there are several important limitations to this approach. For example, the investigated doses should extend from those producing responses well below the EC(50) to those producing ones close to the maximum response, optimally reach steady state response and followed until the response returns to baseline. It is shown that large inter-individual variability on PK-PD parameters will produce biases as well as large imprecision on parameter estimates. It is also clear that extrapolations to dosage routes or schedules other than those used to estimate the parameters should be undertaken with great caution (e.g., in case of non-linearity or complex drug distribution). Consequently, it is advised to apply this approach only when the underlying structural PD and PK are well understood. In any case, K-PD model should definitively not be substituted for the gold standard PK-PD model when correct full model can and should be identified.

Adenosine↗

PubMed2006

Thoracoscopic palliative treatment of malignant pleural effusions: results in 273 patients.

BACKGROUND: The aim of this study was to analyze the results of pleurodesis for malignant pleural effusion performed by surgeons. PATIENTS AND METHODS: A series of 273 patients with malignant pleural effusion underwent thoracoscopy with the aim of performing a palliative pleurodesis. There were 94 males (34.4%) and 175 females (64.1%), ranging in age from 15 to 94 years (mean age: 60.6 years). The effusion was on the right side in 136 patients (49.8%), on the left side in 110 (40.3%), and bilateral in 27 (9.9%). Thoracoscopy was performed under general anaesthesia in all patients. Pleural biopsy was performed in two thirds of the patients (70.7%). Pleurodesis was produced by instillation of 5g of sterile asbestos-free talc; the chest tube was left in place a minimum of 3 days. It was removed when fluid drainage was less than 200 ml/24 h. Patients were usually discharged the day after chest tube removal. RESULTS: There was no intraoperative mortality. Two patients (0.7%) had intraoperative complications; 17 (6.2%) underwent a bilateral pleurodesis, and 10 (3.7%) had a pericardiopleural window. In 32 patients (11.7%) no pleurodesis was done, either because the lung did not properly re-expand (5.2%), or because of suspected infection, e.g., false membranes (1.9%), or because of multiple adhesions (4.6%). Finally, only 241 patients (88.3%) had a talc poudrage at the time of thoracoscopy. Duration of postoperative pleural drainage ranged between 1 and 11 days (mean: 3.64 days). The postoperative hospital stay ranged from 2 to 21 days (mean: 7.1 days). Pleural empyema occurred in 4 patients (1.5%) and was lethal in one patient. The mean follow-up period was 8.39 (7.2 months, and 172 patients had regular follow up. In this group, there were 24 recurrences (14%), 12 of which were treated by repeat pleurodesis. The results were very good in 133 patients (77.3%), acceptable in 35 patients (20.3%), and there was a failure in 4 patients (2.4%). CONCLUSIONS: Results of surgical thoracoscopy for malignant pleural effusion are good, with low morbidity. However, in debilitated patients, bedside talc slurry may be preferable.

Adolescent↗

PubMed2005

[Diagnostic approach to venous thromboembolic disease].

The diagnosis of pulmonary embolism (PE) and deep venous thrombosis (DVT) has long been based on purely clinical grounds. Pulmonary angiography and scintigraphy, as well as venography, reveal the poor diagnostic value of signs and symptoms of PE and DVT, which are now reduced to the role of triggers for these diagnostic tests. The development of simpler, but still imperfect, diagnostic tools (mainly, D-dimer plasma level, venous compression ultrasound, clinical probability of PE or DVT, spiral CT pulmonary angiography) has led to the development of diagnostic strategies, which use combinations of tests, not to provide diagnostic certainty for every patient (presence or absence of clots), but rather to select populations of patients who need treatment and others who can safely remain untreated. Such pragmatic approaches must be validated in appropriate outcome studies. The choice of a diagnostic strategy should depend not only on the strategy's cost-effectiveness in the population under study but also on the local facilities and expertise required for its use.

Cost-Benefit Analysis↗

PubMed2005

Passive or active fluctuations in membranes containing proteins.

We have experimentally investigated the effect of a transmembrane protein, the Ca2+-ATPase, on shape fluctuations of giant vesicles. By using the micropipette method, we have measured a substantial renormalization of the bending modulus due to the presence of proteins in the membrane. Moreover, we have produced the first quantitative measurement of the active force dipole associated with the amplification of the fluctuations when the proteins are activated by adenosine 5'-triphosphate (ATP).

Biological Transport, Active↗

PubMed2004

Proton source size measurements in the eA-->e'ppX reaction.

Two-proton correlations at small relative momentum q were studied in the eA(3He,4He,C,Fe)-->e(')ppX reaction at E(0)=4.46 GeV using the CLAS detector at Jefferson Lab. The enhancement of the correlation function at small q was found to be in accordance with theoretical expectations. Sizes of the emission region were extracted, and proved to be dependent on A and on the proton momentum. The size of the two-proton emission region for He was measured in eA reactions for the first time.

Journal Article↗

PubMed2004

Two-nucleon momentum distributions measured in 3He(e,e'pp)n.

We have measured the 3He(e,e'pp)n reaction at 2.2 GeV over a wide kinematic range. The kinetic energy distribution for "fast" nucleons (p>250 MeV/c) peaks where two nucleons each have 20% or less, and the third nucleon has most of the transferred energy. These fast pp and pn pairs are back to back with little momentum along the three-momentum transfer, indicating that they are spectators. Calculations by Sargsian and by Laget also indicate that we have measured distorted two-nucleon momentum distributions by striking one nucleon and detecting the spectator correlated pair.

Journal Article↗

PubMed2004

Results of thoracoscopic pleural abrasion for primary spontaneous pneumothorax.

BACKGROUND: Several video-assisted techniques have been used to treat primary spontaneous pneumothorax (PSP). The aim of this study was to evaluate the results of thoracoscopic pleural abrasion for PSP. METHODS: From 1991 to 2003, 185 consecutive patients, 143 male and 42 female, aged 15 to 60 years (average 31.6) underwent thoracoscopic pleural abrasion for PSP. The indications for surgery were as follows: a first episode with persistent air leak in 33 patients (17.9%), a recurrent ipsilateral pneumothorax in 122 patients (65.9%), a previous contralateral pneumothorax in 23 patients (12.4%), and recurrence after surgical treatment in seven patients (3.8%). Bullae were resected in 163 patients (88.1%). Mechanical pleural abrasion was performed in all cases. RESULTS: There were no deaths. Intraoperative hemorrhage occurred in three patients. It was controlled via thoracotomy in one patient and via thoracoscopy in two patients. The postoperative complication rate was 8.1% (15/185). Complications included prolonged air leak in eight patients (4.3%), pleural effusion in two (1.1%), extrapleural hematoma in one (0.5%), chest wall infection in one (0.5%), atelectasis in one (0.5%), and hemorrhage in two (1.1%). Postoperative hospital stay ranged between 2 and 17 days (mean, 5). Mean duration of drainage was 3.8 days (range; 1-16). Postoperatively, 111 patients were contacted, with a mean follow-up of 36.5 months. Four of them had a recurrence (3.6%) that did not require reoperation. CONCLUSION: Thoracoscopic pleural abrasion associated with bullae resection is a safe and efficient treatment for PSP. Results remain stable in the long term.

Adolescent↗

PubMed2004

Observation of an exotic baryon with S=+1 in photoproduction from the proton.

The reaction gamma p-->pi(+)K(-)K(+)n was studied at Jefferson Laboratory using a tagged photon beam with an energy range of 3-5.47 GeV. A narrow baryon state with strangeness S=+1 and mass M=1555+/-10 MeV/c(2) was observed in the nK(+) invariant mass spectrum. The peak's width is consistent with the CLAS resolution (FWHM=26 MeV/c(2)), and its statistical significance is (7.8+/-1.0)sigma. A baryon with positive strangeness has exotic structure and cannot be described in the framework of the naive constituent quark model. The mass of the observed state is consistent with the mass predicted by the chiral soliton model for the Theta(+) baryon. In addition, the pK(+) invariant mass distribution was analyzed in the reaction gamma p-->K(-)K(+)p with high statistics in search of doubly charged exotic baryon states. No resonance structures were found in this spectrum.

Journal Article↗

PubMed2004

Fluid membranes exchanging material with external reservoirs.

We investigate the dynamics of a single component fluid bilayer, which exchanges material with the surrounding fluid. We derive covariant equations of motion taking into account solvent permeation, exchange of lipids between solvent and the membrane and discuss the sources of noise in these equations. Different lipid concentrations on both sides of the membrane lead to a non-equilibrium state. We discuss steady states as well as shape instabilities which occur at a critical osmotic-pressure difference.

Biophysics↗

PubMed2003

Measurement of the proton spin structure function g1(x,Q2) for Q2 from 0.15 to 1.6 GeV2 with CLAS.

Double-polarization asymmetries for inclusive ep scattering were measured at Jefferson Lab using 2.6 and 4.3 GeV longitudinally polarized electrons incident on a longitudinally polarized NH3 target in the CLAS detector. The polarized structure function g(1)(x,Q2) was extracted throughout the nucleon resonance region and into the deep inelastic regime, for Q(2)=0.15-1.64 GeV2. The contributions to the first moment Gamma(1)(Q2)= integral g(1)(x,Q2) dx were determined up to Q(2)=1.2 GeV2. Using a parametrization for g(1) in the unmeasured low x regions, the complete first moment was estimated over this Q2 region. A rapid change in Gamma(1) is observed for Q2<1 GeV2, with a sign change near Q(2)=0.3 GeV2, indicating dominant contributions from the resonance region. At Q(2)=1.2 GeV2 our data are below the perturbative QCD evolved scaling value.

Journal Article↗

PubMed2003

Measurement of ep-->e' ppi+ pi- and baryon resonance analysis.

The cross section for the reaction ep-->e(')ppi(+)pi(-) was measured in the resonance region for 1.4<W<2.1 GeV and 0.5<Q2<1.5 GeV(2)/c(2) using the CLAS detector at Jefferson Laboratory. The data show resonant structures not visible in previous experiments. The comparison of our data to a phenomenological prediction using available information on N(*) and Delta states shows an evident discrepancy. A better description of the data is obtained either by a sizable change of the properties of the P13(1720) resonance or by introducing a new baryon state, not reported in published analyses.

Journal Article↗

PubMed2003

First measurement of transferred polarization in the exclusive ep-->e'K+Lambda--> reaction.

The first measurements of the transferred polarization for the exclusive e-->p-->e(')K+Lambda--> reaction have been performed at Jefferson Laboratory using the CLAS spectrometer. A 2.567 GeV beam was used to measure the hyperon polarization over Q2 from 0.3 to 1.5 (GeV/c)(2), W from 1.6 to 2.15 GeV, and over the full K+ center-of-mass angular range. Comparison with predictions of hadrodynamic models indicates strong sensitivity to the underlying resonance contributions. A nonrelativistic quark-model interpretation of our data suggests that the ssmacr; quark pair is produced with spins predominantly antialigned. Implications for the validity of the most widely used quark-pair creation operator are discussed.

Journal Article↗

PubMed2003

Comparative impact of standard approach, FDG PET and FDG dual-head coincidence gamma camera imaging in preoperative staging of patients with non-small-cell lung cancer.

We prospectively compared the impact of the standard approach, of fluorodeoxyglucose positron emission tomography (FDG PET) and of FDG dual-head coincidence gamma camera imaging (DHC) in preoperative staging of patients with non-small-cell lung cancer (NSCLC). In addition to traditional staging, 42 patients were studied with a PET system and a DHC system. The number of lesions detected on DHC and on PET were compared independently of the proof of a tumoural invasion. Then, for the sub-group of lesions with the proof of a tumoural invasion, the sensitivity of the different imaging modalities was compared. Finally, stagings were compared with final staging established by histopathological findings (n=28), additional imaging modalities (n=4), clinical and traditional imaging follow-up over at least 4 months. DHC detected 105 of the 145 lesions considered as pathological on PET (73%, P=0.01), with a concurrence of 89% (NS) in lesions larger than 1.5 cm, and only 17% (P=0.03) in those smaller or equal to 1 cm. Traditional staging detected 87 of the 114 verified tumoural lesions (76%), PET 110/114 (96%, P=0.01 vs traditional staging), DHC 88/114 (77%, NS vs traditional staging, P=0.01 vs PET). PET correctly predicted the N stage in 39/42 (93%) patients, DHC in 38/42 (90%), and computed tomography in 32/42 (76%). PET correctly predicted the M stage in 42/42 (100%) patients, DHC in 41/42 (98%), and traditional staging in 38/42 (90%). Identical NM staging was obtained with DHC and PET in 38/42 (90%) patients. Compared to traditional NM staging, PET correctly up-staged 9/42 (21%) patients and down-staged 3/42 (7%), with one additional false N up-staging. DHC correctly up-staged 7/42 (17%) patients and down-staged 3/42 (7%), with one additional false N down-staging. PET correctly reclassified 4/42 (9.5%) patients from resectable to unresectable and incorrectly reclassified one. DHC correctly reclassified 3/42 (7%) patients without false therapeutic reclassification. Although DHC detected fewer lesions than PET, DHC is a possible alternative to PET since the impact on staging was high as compared with traditional staging and was very similar to that of PET.

Adult↗

PubMed2002

Eta photoproduction on the proton for photon energies from 0.75 to 1.95 GeV.

Differential cross sections for gammap-->etap have been measured with tagged real photons for incident photon energies from 0.75 to 1.95 GeV. Mesons were identified by missing mass reconstruction using kinematical information for protons scattered in the production process. The data provide the first extensive angular distribution measurements for the process above W=1.75 GeV. Comparison with preliminary results from a constituent quark model support the suggestion that a third S11 resonance with mass approximately 1.8 GeV couples to the etaN channel.

Journal Article↗

PubMed2002

Q2 Dependence of quadrupole strength in the gamma*p --> Delta(+)(1232) --> p pi(0) transition.

Models of baryon structure predict a small quadrupole deformation of the nucleon due to residual tensor forces between quarks or distortions from the pion cloud. Sensitivity to quark versus pion degrees of freedom occurs through the Q2 dependence of the magnetic (M1+), electric (E1+), and scalar (S1+) multipoles in the gamma*p-->Delta(+)-->p pi(0) transition. We report new experimental values for the ratios E(1+)/M(1+) and S(1+)/M(1+) over the range Q2 = 0.4-1.8 GeV2, extracted from precision p(e,e(')p)pi(0) data using a truncated multipole expansion. Results are best described by recent unitary models in which the pion cloud plays a dominant role.

Journal Article↗

PubMed2002

First measurement of the double spin asymmetry in (-->)e(-->)p-->e(prime)pi(+)n in the resonance region.

The double spin asymmetry in the (-->)e(-->)p --> e(prime)pi(+)n reaction has been measured for the first time in the resonance region for four-momentum transfer Q2 = 0.35-1.5 GeV(2). Data were taken at Jefferson Lab with the CLAS detector using a 2.6 GeV polarized electron beam incident on a polarized solid NH3 target. Comparison with predictions of phenomenological models shows strong sensitivity to resonance contributions. Helicity-1/2 transitions are found to be dominant in the second and third resonance regions. The measured asymmetry is consistent with a faster rise with Q(2) of the helicity asymmetry A1 for the F(15)(1680) resonance than expected from the analysis of the unpolarized data.

Journal Article↗

PubMed2002

[Acute respiratory failure due to Gemcitabine-induced pulmonary toxicity].

Gemcitabine is a therapeutic agent that has been recently employed in the treatment of various cancers. Pulmonary toxicity has rarely been described. We report a case of a patient treated with Gemcitabine who developed acute respiratory symptoms related to a hypersensitivity pneumonia. Despite a severe clinical and radiological presentation, the outcome was favorable with corticosteroid treatment. In the event of respiratory symptoms in patients receiving Gemcitabine further investigations (chest X-ray, thorax CT-scan, bronchoalveolar lavage) are indicated. In view of the severity of pulmonary toxicity that can be caused by Gemcitabine, re-introduction of treatment is not recommended. We compare our case with other published cases of Gemcitabine-induced pulmonary toxicity.

Acute Disease↗