Search PubMed⌕ Search

Biomedical subjects

P Carpentier

Publications and source records attributed to P Carpentier.

At least 19 recordsLinked to original sources

Validation of a chemical osteoarthritis model in rabbit temporomandibular joint: a compliment to biomechanical models.

To explore degenerative mechanisms occurring in the temporomandibular joint (TMJ), a chemical model of knee joint osteoarthritis using sodium mono-iodoacetate injection was transposed to the TMJ. Twelve New Zealand rabbits were used to document the effect of this drug on the TMJ. Eight rabbits underwent bilateral iodoacetate injection in the disco-condylar compartment while 4 served as controls. Rabbits were sacrificed at 10, 20, 30 and 40 days and joints studied by histology. Severity of the damage was time dependent and the use of iodoacetate allowed the observation, within a few weeks, of every osteoarthritic stage usually described in the literature. This study showed that the TMJ has a specific response to the degenerative process. This response was characterized by (i) thickening and fibrillation of the cartilage at the periphery of the lesion, tending to reduce mechanical stress in the lesional area and (ii) chondrocyte migration under areas where subchondral bone surface was locally destroyed. The extracellular matrix containing chondrocyte clusters and prechondrocytes dived around the bony defect and proceeded below the necrotic bone to promote the eviction of bony fragments into the joint cavity, pushing them up while the thickness of chondrocyte rows increased below. This could be interpreted as a repairing attempt due to the specific potential of fibrocartilage proliferative cells.

Alkylating Agents↗

[Sub acute ischemia of a lower limb in a patient with juvenile peripheral arterial disease and arterial cocaine toxicity].

A 35-year-old woman was hospitalized for subacute ischemia of the left leg following an intermittent claudication for some weeks. She also presented paleness and coldness of both hands. The radial pulses could not be palpated. Smoking was the only cardiovascular risk factor. Duplex ultrasonography and angiography revealed a left popliteal thrombus combined with low diameter leg arteries and in the upper limbs stenosis of the left radial artery and thrombosis of the right radial artery. Search for a metabolic, embolic or thrombophilic etiology was negative. More minute history taking revealed use of cannabis and recent nasal administration of cocaine. Her condition improved with heparin therapy except for the upper limbs with ischemia of the hands and disabling Raynaud's phenomenon. This report highlights the combined arterial toxicity of drugs often used together by drug addicts. The association of cannabis use and tobacco smoking is not rare in patients with Buerger-like juvenile arteriopathy and cocaine may provoke peripheral vascular disease by embolism or in situ thrombosis. Interrogation of a patient presenting with Buerger-like peripheral arterial disease should insist on detecting use of drugs in association with tobacco smoking.

Adult↗

[Sentinel node biopsy without systematic axillary dissection: study about 1000 procedures].

OBJECTIVE: To assess daily practice of 1000 sentinel node (SN) biopsies in breast cancer. PATIENTS AND METHOD: Prospective review of 1000 consecutive sentinel node biopsies between February 2001 and June 2004. Analyses concerned technical aspects of sentinel node detection, pathologic results of the tumor and sentinel node, treatment and follow-up. RESULTS: Nine hundred and seventy-eight SN were detected (98.7%). In univariate analyses, age, pathologic tumor size (20 mm) and method of detection (blue dye or isotopic vs. combined) were statistically significant. One hundred and fifty-six cases (16%) underwent immediate axillary dissection (AD), whereas 116 (12%) had a delayed AD. There were 923 invasive or micro-invasive carcinoma with detected SN: 282 SN (30.5%) were involved, either with macrometastases (166) or with micrometastases (116), 34% had positive non-sentinel node. Age and metastasis size were predictive for AD involvement. Sixteen percent of micrometastatic SN had positive AD, there was no predictive factor for axillary involvement. After a median follow-up of 20 months, there were 4 axillary recurrences: 1 (0.1%) after negative SN without AD, 1 (0.1%) after positive SN with positive AD, 1 (4.3%) after micrometatastatic SN without AD, and 1 (8.3%) after macrometastatic SN without AD. There were 55 ductal carcinoma in situ and 54 micro-invasive cancer: positive SN (with negative AD) were detected in only 2 cases (2.3%). There were initially 112 ductal carcinoma in situ diagnosed by percutaneaous biopsy, 25 of them (22%) had invasive disease on definitive histology. Among there, 12 had involved SN (with 4 positive AD). DISCUSSION AND CONCLUSION: With a high detection rate and low recurrence rate, SN biopsy is considered in our institute as a reliable procedure and is used to evaluate regional nodal status of early breast cancer. Thus, 70% of AD can be omitted.

Adult↗

[Optimizing history taking for evaluating the risk of venous thromboembolism: the OPTIMEV study].

UNLABELLED: Venous thromboembolism (VTE) is a frequent disease and remains a major cause of mortality and morbidity among our patients. During the 20 past years, clinical description, diagnostic tools, and treatment have changed dramatically. Most published data describing risk factors for VTE no longer apply to the patients seen in daily practice. We present here the rationale, aims, and methodology of the OPTIMEV Study (OPTimisation de l'Interrogatoire pour la Maladie thromboEmbolique Veineuse). RATIONALE: Risk factors for VTE are numerous, complex and interactions between them and their clinical importance is difficult to measure (table I). For example, odds ratios for VTE recurrence vary greatly across longitudinal studies. We searched the National Library of Medecine (PubMed) and the Amedeo website using the following keywords: "venous thromboembolism", "pulmonary embolism", "deep vein thrombosis", "risk factors". We selected 84 relevant articles published between 1972 and 2005. Based on this literature analysis, we identified the following major risk factors: VTE recurrence, surgery, cancer, immobilization, age, biological factors. For these factors, data are lacking and some questions are proposed. OBJECTIVES: The broad objective of the study is to better evaluate clinical risk factors that fit today's practice against VTE. Specific aims are: 1) to determine whether risk factors are different between proximal and distal deep vein thrombosis (DVT); 2) to develop and prospectively validate a new prediction rule for outpatients. The primary hypothesis is that careful assessment of VTE recurrence, adequate surgical thromboprophylaxis, cancer staging, and varicose vein stratification according to the CEAP classification, is mandatory for accurate evaluation of thromboembolic disease risk. METHODS: We conducted a multicenter, prospective, cohort study of 10000 patients. Enrollees are inpatients and outpatients presenting with a clinical suspicion of VTE in Emergency Departments and outpatient clinics in France. 4173 patients have been enrolled at this time (Figure 2). All eligible patients are enrolled during a selected period of time through different seasons. Data are collected by physicians in charge of the patients using an electronic case recording form. Collected data include baseline characteristics, risk factors, results of diagnostic investigations. Outcome measures obtained through telephone interview at 3 and 12 months include cancer diagnosis, VTE recurrence, haemorrhagic events, treatments, death. Univariate and multivariate analysis will be performed using multilevel logistic regression. The study organization is performed by the Centre d'Investigation Clinique de Grenoble and is sponsored by the French Society of Vascular Medicine. First results, to be published in 2006, will allow development of new prediction rules for VTE diagnosis.

Age Factors↗

Veno-active drugs in the management of chronic venous disease. An international consensus statement: current medical position, prospective views and final resolution.

BACKGROUND: Veno-active drugs (VAD) have effects on edema and symptoms related to chronic venous disease (CVD), especially so-called venous pain. VAD's effectiveness, although well established, is regularly debated. OBJECTIVE: Our purpose was to select all randomized controlled trials (RCTs) and meta-analyses devoted to VAD and symptoms in CVD, to submit them to a group of international experts in CVD and to vote with secrete ballot to determine the level of efficacy of each drug, according to EBM (Evidence-Based Medicine) rules and critical analysis. METHODS: Publications in any language devoted to VAD and venous symptoms were searched for in different databanks and submitted to the experts prior to the meeting. RESULTS: 83 papers were analyzed, including 72 RCTs or meta-analyses. Experts determined the level of EBM of each drug, according to the literature and personal experience, using 3 levels of recommendation, A, B and C (from large RCTs to non-randomized trials). CONCLUSIONS: VAD are effective and may be applied in CVD when symptomatic, from C0s to C6s. However, etiological treatment of venous reflux and venous hypertension has always priority. In some cases VAD may replace compression and/or complement its effects. If respecting these prerequisites, VAD are safe and effective.

Chronic Disease↗

Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist.

OBJECTIVE: Recurrent digital ulcers are a manifestation of vascular disease in patients with systemic sclerosis (SSc; scleroderma) and lead to pain, impaired function, and tissue loss. We investigated whether treatment with the endothelin receptor antagonist, bosentan, decreased the development of new digital ulcers in patients with SSc. METHODS: This was a randomized, prospective, placebo-controlled, double-blind study of 122 patients at 17 centers in Europe and North America, evaluating the effect of treatment on prevention of digital ulcers. The primary outcome variable was the number of new digital ulcers developing during the 16-week study period. Secondary assessments included healing of existing digital ulcers and evaluation of hand function using the Scleroderma Health Assessment Questionnaire. RESULTS: Patients receiving bosentan had a 48% reduction in the mean number of new ulcers during the treatment period (1.4 versus 2.7 new ulcers; P = 0.0083). Patients who had digital ulcers at the time of entry in the study were at higher risk for the development of new ulcers; in this subgroup the mean number of new ulcers was reduced from 3.6 to 1.8 (P = 0.0075). In patients receiving bosentan, a statistically significant improvement in hand function was observed. There was no difference between treatment groups in the healing of existing ulcers. Serum transaminase levels were elevated to >3-fold the upper limit of normal in bosentan-treated patients; this elevation is comparable with that observed in previous studies of this agent. Other side effects were similar in the 2 treatment groups. CONCLUSION: Endothelins may play an important role in the pathogenesis of vascular disease in patients with SSc. Treatment with the endothelin receptor antagonist bosentan may be effective in preventing new digital ulcers and improving hand function in patients with SSc.

Activities of Daily Living↗

[Pulmonary arterial hypertension in systemic sclerosis: definition of a screening algorithm for early detection (the ItinérAIR-Sclérodermie Study)].

PURPOSE: Pulmonary arterial hypertension (PAH) is a severe complication of scleroderma. Its prevalence varies from 5% to 35% in the literature. A systematic yearly screening is recommended for early detection and management of PAH, but no precise algorithm is yet available. METHODS: From literature analysis as well as evaluation of medical needs and practices, a multidisciplinary board of experts proposed an algorithm for the screening of PAH in scleroderma. RESULTS: This algorithm is based on a precise Doppler echocardiography methodology for the purpose of screening scleroderma patients for PAH. Patients are considered as being at high or low risk of PAH depending on the maximal tricuspid regurgitation velocity. High-risk patients undergo right heart catheterization for confirmation of the diagnosis of PAH. A French multicenter transversal observational study ("ItinérAIR Sclérodermie") will be conducted in 21 hospital centers in France and involved 100 investigators organized as multidisciplinary networks. FUTURE PROSPECTS: Final results will provide confirmation that the screening algorithm is applicable in a real world setting, as well as a better knowledge of the prevalence of PAH in the various sub-groups of scleroderma patients, of the risk profile for PAH and of the value of DLCO as a predictive factor for PAH, and will support elaboration of precise screening guidelines.

Algorithms↗

[Impact of an education program on patient behaviour favoring prevention of drug-related adverse events: a pilot study in patients receiving oral anticoagulants for thromboembolic venous disease].

OBJECTIVE: Adverse events related to oral anticoagulants represent a major public health problem. Including patient education as part of the prevention strategy could contribute to improved effectiveness and safer use of drugs. The present study aimed at evaluating the outcomes of a patient education program inspired by recommendations from French Health Authorities (AFSSAPS) and based on an "individual guidance" approach. METHOD: The study was conducted in two groups of hospitalized patients treated with oral anticoagulants for thromboembolic disease. Each patient in the first (intervention) group attended an individual teaching session conducted at discharge by a trained pharmacist. Patients in the second (control) group were given usual care. These two groups were compared at inclusion (before intervention) and three months later. The outcomes considered were the acquisition of: 1) knowledge, 2) risk anticipation and compliance behaviours characterized by the stability of INR and the incidence of hemorrhagic episodes during the period of observation. RESULTS: Fifty-nine patients (average age 65 years) were included (29 in the intervention group and 30 in the control group). Three months after the intervention, the intervention group exhibited 1) better knowledge (higher rate of restitution of treatment-related information--name of the drug, administration plan, targeted range for INR (...), interpretation of INR results (p<0.05), management of a specific scenario where INR declines concomitant to elevation of anticoagulant dose (p<0.05)); 2) higher rates of relevant behaviours (p<0.05)--in the event of a missed dose, anticipating an event with a high risk of bleeding, dealing with signs of overdose--and higher compliance profile (ns) (stability of INR, and number of hemorragic episodes). A multivariate model integrating the potential explanatory variables for frequency of hemorrhagic episodes at 3 months (demographic data, history of thrombotic disease, INR stability, reference group (intervention/control)), showed that the only variable significantly associated with frequency of bleeding events was the reference group of the patient (p=0.05; odds-ratio=4.5, interval of confidence: [1-21]). CONCLUSION: Multivariate analysis demonstrated that the probability of developing a hemorrhagic event when taking an oral anticoagulant is on average 4-fold greater in patients given usual care than in patients given individual guidance a pharmacist. A larger randomized trial is currently under way in the Rhône-Alpes region, France, to validate these exploratory results.

Aged↗

Validation of a clinical guideline on prevention of venous thromboembolism in medical inpatients: a before-and-after study with systematic ultrasound examination.

BACKGROUND: Clinical practice guidelines on prevention of venous thromboembolism in medical inpatients have been implemented in various settings, although few studies have assessed their impact on venous thromboembolism events. OBJECTIVE: To determine whether the implementation of a locally developed guideline is followed by changes in the rate of deep vein thrombosis. DESIGN: A before-and-after study consisting in two "1-day" cross-sectional studies. SETTING: Thirteen adult medical wards in a teaching hospital in France. SUBJECTS: All the patients hospitalized on the day of the cross-sectional study. INTERVENTION: A clinical guideline integrating scientific evidence and data on target medical providers' practices was developed by a local expert panel and implemented through a multifaceted intervention. MEASUREMENTS: Prevalence of deep vein thrombosis detected by systematic ultrasound examination. RESULTS: The study included 338 patients in the preintervention sample and 340 in the postintervention sample. The prevalence of deep vein thrombosis decreased from 9.5% (95% CI, 6.6-13.1) in the preintervention sample to 3.2% (95% CI, 1.6-5.7) in the postintervention sample (P < 0.01). The decrease in the rate of thrombosis involved all deep veins of the lower limbs and remained significant after adjustment for risk factors (adjusted odds ratio = 0.47, 95% CI, 0.32-0.70). No additional cases of pulmonary embolism or deep vein thrombosis were reported either on the day of the study or in the following 2 days. CONCLUSIONS: Active implementation of a clinical practice guideline directed at medical providers (doctors, nurses and physical therapists) can be followed by a significant decrease in prevalence of deep vein thrombosis.

Aged↗

Direct phasing at low resolution of a protein copurified with human paraoxonase (PON1).

In this paper, the low-resolution structure of a previously unknown protein copurified with human paraoxonase (PON1) is reported. The structure of this protein was very difficult to solve using classical crystallographic methods. Progress was made using a new phasing method based on topological analysis. From the experimental point of view, this method has the advantage of requiring only a simple low-resolution X-ray data set. The program used and the different steps of the data-processing and phasing procedure are described. The results provided an insight into the failure of previous molecular-replacement attempts. The low-resolution shape of the protein which was presented with confidence is compared with and confirmed by the structure at 1.8 A solved subsequently using classical methods. This work shows that this direct-phasing method could be used systematically in difficult cases: it provides low-resolution structural information comparable with that obtainable by electron microscopy.

Aryldialkylphosphatase↗

A randomized study comparing epirubicin in a 4-weekly versus a weekly intravenous regimen in patients with metastatic, hormone resistant, prostatic carcinoma: effects on health related quality of life.

The treatment of hormone resistant prostate cancer) with epirubicin 25 mg/m(2)(Epi25) on a weekly intravenous regimen may be better in terms of health related quality of life (HRQOL) than with 100 mg/m(2)(Epi100) on a 4-weekly regimen. A total of 79 patients who filled out the EORTC-QLQ-C30 questionnaire for the assessment of HRQOL could be evaluated. Compared with the baseline, no changes in HRQOL function scales or significant changes in the following HRQOL symptom scales were found. The Epi25 group reported less pain during the first 3 months and the Epi100 group more dyspnoea after 4 weeks and less pain and less insomnia but more loss of appetite after 8 weeks. In both groups, toxicity was comparable, except for World Health Organisation grade II-III alopecia occurring in 82% in the Epi100 versus 31% in the Epi25 group. There were no significant differences between groups in response rates and survival. In this study, HRQOL was not improved which is in line with other studies using only epirubicine. Epirubicin as single agent therapy should not be used in future treatment of patients with HRPC.

Adult↗

X-ray-induced debromination of nucleic acids at the Br K absorption edge and implications for MAD phasing.

Multi-wavelength anomalous dispersion (MAD) using brominated derivatives is considered a common and convenient technique for solving chemically synthesized nucleic acid structures. Here, it is shown that a relatively moderate X-ray dose (of the order of 5 x 10(15) photons mm(-2)) can induce sufficient debromination to prevent structure determination. The decrease in bromine occupancy with radiation dose can be accounted for by a simple exponential, with an estimated rate constant at the absorption-peak wavelength, 7.4 (0.8) MGy, that is not significantly different from its value at the absorption-edge wavelength, 9.2 (2.6) MGy (the given e.s.d.s assess the relative closeness of the two values, not their absolute accuracy, which is probably worse). Chemically, these results (and others) are consistent with bromine cleavage resulting from direct photodissociation and/or from the action of free electrons, rather than from the action of hydroxyl radicals originating from water dissociation. The free bromine species (Br(-)) diffuse too quickly, even in amorphous ice around 100 K, to allow the determination of a diffusion coefficient. From a practical point of view, it is suggested that a single data collection with a crystal consisting of iodinated instead of brominated derivatives could provide both anomalous scattering and SIR phase information by the progressive cleavage of iodine.

Bromine↗

FIP: a highly automated beamline for multiwavelength anomalous diffraction experiments.

FIP is a French Collaborating Research Group (CRG) beamline at the European Synchrotron Radiation Facility (ESRF) dedicated exclusively to crystallography of biological macromolecules, with a special emphasis on multiwavelength anomalous diffraction data collection in the 0.7-1.81 A wavelength range. The optics, consisting of long cylindrical grazing-angle mirrors associated with a cryocooled double-crystal monochromator, delivers an optimal beam in the corresponding energy range. The high level of automation, which includes automated crystal centring, automated data-collection management and data processing, makes the use of this beamline very easy. This is illustrated by the large number of challenging structures that have been solved since 1999.

Automation↗

Major intra-abdominal complications following extracorporeal shockwave lithotripsy (ESWL) in a patient with Ehlers-Danlos syndrome.

A retroperitoneal bleeding is an unusual complication of extracorporeal shockwave lithotripsy (ESWL), which can be treated in a conservative way most of the time. However, an intra-abdominal bleeding after ESWL is extremely rare, which can cause life-threatening situations and requires an immediate intervention. Probably, only patients with a certain tissue fragility or connective tissue disorder are at risk to develop such an intra-abdominal bleeding. We present a case of a serious intra-abdominal bleeding due to a rupture of the vena mesenterica superior in an Ehlers-Danlos patient, evoked by an ESWL.

Abdomen↗

Beneficial effects of TCP on soman intoxication in guinea pigs: seizures, brain damage and learning behaviour.

Poisoning with the potent nerve agent soman produces a cascade of central nervous system (CNS) effects characterized by severe convulsions and eventually death. In animals that survive a soman intoxication, lesions in the amygdala, piriform cortex, hippocampus and thalamus can be observed. In order to examine the mechanisms involved in the effects of soman and to evaluate possible curative interventions, a series of behavioural, electrophysiological and neuropathological experiments were carried out in the guinea pig using the NMDA antagonist N-[1-(2-thienyl)cyclohexyl] piperidine (TCP) in conjunction with atropine and pyridostigmine. The NMDA antagonist TCP appeared to be very effective in the treatment of casualties who suffered from soman-induced seizures for 30 min: (i)Seizures were arrested within minutes after the TCP injection, confirmed by quantitative electroencephalogram (EEG), after fast Fourier analysis. Three hours after TCP the quantitative EEGs were completely normal in all frequency bands and remained normal during the entire 3-week intoxication period. The power shift to the lower (delta) frequency bands, indicative for neuropathology and found in control animals intoxicated only by soman, was not observed in the soman-TCP group. (ii)The gross neuropathology found in soman control animals within 48 h after soman was prevented in soman-TCP animals and was still absent in 3-week survivors. Instead, ultrastructural changes were observed, indicative of defense mechanisms of the cell against toxic circumstances. (iii)Twenty-four hours after soman, soman-TCP animals were able to perform in the shuttle box and Morris water maze. The beneficial effects of TCP on the performance in these tests during the 3-week intoxication period were very impressive, notwithstanding (minor) deficits in memory and learning. (iv)The increase in excitability after TCP was confirmed by an increase in the acoustic startle response. Taken together, these results confirmed the involvement of NMDA receptors in the maintenance of soman-induced seizures and the development of brain damage. They underline the current hypothesis that cholinergic mechanisms are responsible for eliciting seizure activity after soman and that, most likely, the subsequent recruitment of other excitatory neurotransmitters and loss of inhibitory control are responsible for the maintenance of seizures and the development of subsequent brain damage.

Animals↗

Effects of thienylphencyclidine (TCP) on seizure activity and brain damage produced by soman in guinea-pigs: ECoG correlates of neurotoxicity.

The capacity of thienylcyclohexylpiperidine (TCP), a non-competitive blocker of the N-methyl-D-aspartate (NMDA) receptor, to counteract the convulsant, lethal, and neuropathological effects of 2 x LD50 of soman (an irreversible inhibitor of cholinesterase) was investigated in guinea-pigs treated by pyridostigmine and atropine sulphate. The effects of a weak dose of TCP (1 mg/kg) used in the present study globally reproduced those previously obtained with a higher dose (2.5 mg/kg; [Neurotoxicology 15 (1994) 837]): TCP was again most protective when given curatively within the first hour of soman-induced seizures. In this condition, (a) paroxysmal activity ceased in 10-20 min, (b) all the animals survived, (c) the majority of them recovered remarkably well and did not show any brain damage 24 h after the intoxication, and (d) the minimal duration of seizure activity normally required for producing soman-induced brain damage in other pharmacological environments was increased from 10 to 40 min to 80 min. Strikingly, when TCP was given 120 min after seizure onset, it failed to show any anticonvulsant activity but still provided neuroprotection in the hippocampus. The present study also gives additional evidence (see [Neurotoxicology 21 (4) (2000) 521]) that in soman poisoning, (a) the development of brain damage depends on the occurrence of ECoG seizures, (b) the topographical distribution of lesions depends on seizure duration, and (c) an increase of the relative power in the lowest (delta) frequency band might be a reliable marker of neuronal degradation. All these findings confirm that (a) glutamatergic NMDA receptors are involved in the mechanisms of soman-induced seizures and brain damage, (b) non-competitive antagonists of NMDA receptors might be promising candidates for post-treatment of soman poisoning, and (c) ECoG parameters from ECoG tracings and power spectrum might serve as useful external predictors for soman-induced neuropathological changes.

Animals↗