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Biomedical subjects

P Guillot

Publications and source records attributed to P Guillot.

At least 19 recordsLinked to original sources

Improved voltage transfer coefficients for nonconductive materials in radiofrequency glow discharge optical emission spectrometry.

In radiofrequency glow discharge emission spectrometry (RF-GDOES), the excitation voltage used to create the plasma is applied to the back or front end of the sample to be analyzed. In this paper we focus on back-applied voltage systems (a configuration that represents about half of the instruments available on the market), and on applied voltage problems (the power coupling efficiency and materials analysis are beyond the scope of this study). In the RF-GDOES of nonconductive samples, a voltage drop develops inside the material. The voltage transfer coefficient is defined as the ratio between the peak voltage in front of the sample (facing the plasma) and the peak voltage applied to the back of the sample. In this work, we show that it is possible to increase the voltage transfer coefficient by increasing the capacitance of the sample. The capacitance of a given nonconductive material depends on its surface, its thickness and its permittivity. Increasing the voltage transfer coefficient permits higher power deposition in the plasma. This study is based on an electrical equivalent circuit for the discharge device, which takes into account the sample and reactor capacitances as well as the voltage probes used for the measurements. This circuit, when modeled by a commercial electrical circuit simulator, gives the voltage transfer coefficient as a function of the sample capacitance. Different approaches to increasing the sample capacitance and their influence on the voltage transfer coefficient are presented and related to the 750.4 nm argon line intensity, which is correlated to the electron density.

Journal Article↗

Selection of two-phase flow patterns at a simple junction in microfluidic devices.

We study the behavior of a confined stream made of two immiscible fluids when it reaches a T junction. Two flow patterns are witnessed: the stream is either directed in only one sidearm, yielding a preferential flow pathway for the dispersed phase, or splits between both. We show that the selection of these patterns is not triggered by the shape of the junction nor by capillary effects, but results from confinement. It can be anticipated in terms of the hydrodynamic properties of the flow. A simple model yielding universal behavior in terms of the relevant adimensional parameters of the problem is presented and discussed.

Journal Article↗

A prospective study of the incidence of complications associated with dermatological surgery.

BACKGROUND: Dermatological surgery is a relatively new and expanding subspecialty within dermatology. Little information is available about complications in this kind of surgery in the European setting. OBJECTIVES: The aim of this study was to assess the incidence of anaesthetic, haemorrhagic and infectious complications in dermatological surgery and to highlight the factors associated with these complications. METHODS: Data were collected prospectively over a 3-month period for all surgical procedures performed by a network of dermatologists (n = 84 dermatologists) in France, including the excision of all benign or malignant tumours but excluding sebaceous cysts and pyodermas. Information was collected regarding dermatologists, patients, procedures and complications. RESULTS: A total of 3788 surgical procedures were available for review; 236 complications, mostly minor, occurred in a total of 213 surgical procedures (6%), bleeding being the most common (3%). Vaso-vagal syncope was the main anaesthetic complication (51 of 54). Infectious complications occurred in 79 patients (2%). Superficial suppuration accounted for 92% of surgical site infections. Only one patient had a systemic infection. Complications requiring additional antibiotic treatment or repeat surgery accounted for only 22 cases of 3788 (1%). No statistically significant correlation was found with the characteristics of the dermatologists, especially with respect to their training or amount of surgical experience. Similarly, no link could be established between complications and surgical conditions. Multivariate analysis showed that anaesthetic or haemorrhagic complications were independent factors for infectious complications. Sex, administration of an anticoagulant or immunosuppressant, type of procedure performed and duration exceeding 24 min were independent factors for haemorrhagic complications. CONCLUSIONS: This study shows a low rate of complications associated with dermatological surgery performed by dermatologists under local anaesthesia on an outpatient basis.

Adolescent↗

[Alternative activation of antigen-presenting cells: concepts and clinical relevance].

Lymphocytes do not just act as immunological effector cells, but also play an important role in the regulation of the immune response. They are able to induce or suppress inflammatory reactions and this balancing function is reflected in the well-known Th1/Th2 concept. Lymphocytes depend on antigen presenting cells (APC) for induction of differentiation and specific activation mediated by antigen capture, processing and presentation. Thus, APC represent a link between innate and acquired immunity. In parallel to the Th1/Th2 dichotomy, APC may be subdivided into (a) pro-inflammatory, classically activated APC such as mature dendritic cells and IFN-gamma-activated effector macrophages, and (b) into anti-inflammatory, alternatively activated APC such as IL-10-activated immature dendritic cells and IL-4-induced suppressor macrophages. Alternatively activated APC may mediate induction and maintenance of tolerance towards allergens and environmental substances, control the course of inflammatory reactions, and participate in healing processes by enhancing angiogenesis. Malignant tumors and certain infectious agents may misuse alternatively activated APC for their purposes, thereby requiring counter-action by Th1 lymphocytes and classically activated APC. The concept of alternative activation thus confirms the important role of APC in maintaining the balance between induction and suppression of both inflammation and immunity and it opens new perspectives for the development of specific immunotherapeutic approaches.

Animals↗

Alternatively activated macrophages differentially express fibronectin and its splice variants and the extracellular matrix protein betaIG-H3.

Alternative activation of macrophages, induced by Th2 cytokines and glucocorticoids, is essential for the proper functioning of anti-inflammatory immune reactions. To this end, alternatively activated macrophages (aaMPhi) express a not yet fully unravelled set of genes including cytokines such as alternative macrophage activation-associated CC-chemokine (AMAC)-1 and pattern recognition molecules such as the scavenger receptor CD163. In order to further characterize the molecular repertoire of aaMPhi, differential gene expression was analyzed by combining subtractive suppression cloning and differential hybridization. We show here that aaMPhi induced by interleukin (IL)-4 overexpress the prototype extracellular matrix (ECM) protein fibronectin on the mRNA and protein level. This overall increase is accompanied by a shift in fibronectin splice variants from an embryonic to a mature pattern. In addition, the expression of another ECM protein, betaIG-H3, is also upregulated by IL-4 in aaMPhi. In contrast to IL-4 and in line with its inhibitory effect on wound healing, dexamethasone exerts a strongly suppressive effect on fibronectin and betaIG-H3 expression. In conclusion, overexpression of ECM proteins induced by IL-4 in macrophages suggests that aaMPhi may be involved in ECM deposition and tissue remodelling during the healing phase of acute inflammatory reactions and in chronic inflammatory diseases.

Alternative Splicing↗

Further genetic analysis of two autosomal dominant mouse eye defects, Ccw and Pax6(coop).

PURPOSE: The work forms part of a major project to study the genetics of mouse cataract mutants found during the course of mutagenesis experiments. The long-term aim is to find the underlying gene mutation in each cataract mutant. Here we report further studies of the mutant cataract and curly whiskers (Ccw), previously mapped to Chromosome 4, and also investigations of the corneal opacity (Coop) mutant, which is shown to involve a mutation in the Pax6 gene. METHODS: For Ccw, the methods included mapping relative to microsatellite markers and histological studies. For the Coop mutant, breeding methods were used to show that Coop was allelic with Pax6. The Pax6 coding region in the mutant was then sequenced. RESULTS: The Ccw locus was mapped to approximately position 45cM on the consensus map of Chr 4. Histologically, progressive degeneration of the lens was seen. In the Coop mutant, a base-pair change C->T was found at position 1033 in the Pax6 gene, which created a stop codon leading to premature termination of translation, and to a truncated Pax6 protein. CONCLUSIONS: The phenotype in Ccw/+ heterozygotes involves a new type of lens degeneration in the mouse. On the basis of the phenotype and the locus position, no candidate gene has yet been identified. The Pax6coop mutant differs in phenotype from known null alleles of Pax6, implying that it is a hypomorph.

Animals↗

Pseudoexons and regulatory elements in the genomic sequence of the beta-chemokine, alternative macrophage activation-associated CC-chemokine (AMAC)-1.

Recently, the authors reported the cloning of a novel human CC chemokine of alternatively activated macrophages (AMAC-1), whose expression is induced by Th2-associated cytokines such as interleukin 4 (IL-4), IL-13 and IL-10; vice versa, AMAC-1 expression is inhibited by Th1-associated cytokines such as interferon gamma (IFN-gamma). In order to study the genomic organization and transcriptional regulation of the AMAC-1 gene, genomic clones were isolated by screening a human lambda genomic library. Sequencing of a clone with a 1.7-kb insert gave a partial genomic sequence for the AMAC-1 gene. The complete AMAC-1 genomic sequence was obtained by bioinformational methods and the whole region spanning the AMAC-1 gene was verified by PCR amplification of subfragments and sequencing. The AMAC-1 gene consists of three exons. Whereas exons 2 and 3 were separated by a small intron of 411 bp, exon 1 and exon 2 were separated by 6 kb of non-translated genomic sequence containing two pseudoexons that are not expressed although they feature intact exon/intron boundaries and complete open reading frames. In order to allow a detailed analysis, a 2.7-kb fragment containing the promoter region and the first exon of AMAC-1 gene was cloned into a reporter gene construct. In the AMAC-1 promoter, two possible transcription start points were identified. In addition, several putative regulatory sequences for IL-4- and IFN-gamma-dependent transcriptional pathways were found including STAT6 and STAT1 binding sites as well as several AP-1 and C/EBP elements. Interestingly, a combined STAT6/STAT1 binding element is located in the direct vicinity of the first putative transcription start point. Competitive binding of IL-4-induced STAT6 versus IFN-gamma-induced STAT1 to this site may explain the antagonistic effects these cytokines exert on AMAC-1 expression.

Amino Acid Sequence↗

Intraarticular glucocorticosteroid injection into the lateral atlantoaxial joint under fluoroscopic control. A retrospective comparative study in patients with mechanical and inflammatory disorders.

OBJECTIVES: To evaluate the overall efficacy in various disorders of glucocorticoid injection into the lateral atlantoaxial joints, performed via the posterior route under fluoroscopic control. METHODS: Retrospective study of 26 patients including 16 (19 injections) with mechanical disorders and ten (16 injections) with inflammatory disorders. RESULTS: The response rate was 69.3%, the mean pain scale score decrease was 52.3 +/- 40.1%, and the mean duration of pain relief was 8.1 +/- 11.8 months. All three parameters were significantly (P < 0.005) better in the subgroup with inflammatory disorders than in the subgroup with mechanical disorders (response rate, 100% vs 50%; pain scale score decrease, 80 +/- 27% vs 34.2 +/- 40%, and pain relief duration, 16.9 +/- 14.9 months vs 24.5 months). A single patient developed a side effect (moderately severe hypertension). CONCLUSION: Glucocorticoid injection into the lateral atlantoaxial joints is a valid treatment alternative in patients who fail to respond to conventional noninvasive therapy.

Aged↗

Alternative versus classical activation of macrophages.

In parallel to the Th1/Th2 paradigm, antigen-presenting cells (APC) are divided into classically activated APC (dendritic cells/effector macrophages) and alternatively activated APC (IL-4-induced, alternatively activated macrophages/IL-10-induced, immature dendritic cells). Alternatively activated APC share a special molecular repertoire including receptors of innate immunity with broad specificity for foreign antigen and anti-inflammatory cytokines such as IL-1Ra and alternative macrophage activation-associated CC-chemokine-1. Alternatively activated APC mediated tolerance and downregulated inflammation. Abuse of alternatively activated APC in support of infectious susceptibility or tumor immune escape is counteracted by the classical pathway. Thus, classically and alternatively activated APC secure the balance between proinflammatory and anti-inflammatory immune reactions.

Animals↗

Is it possible to predict the efficacy at discharge of inhospital rheumatology department management of disk-related sciatica? A study in 150 patients.

OBJECTIVES: To identify criteria for predicting the outcome at discharge in patients scheduled for inhospital treatment of disk-related sciatica. PATIENTS AND METHODS: We studied 150 rheumatology department patients admitted for disk-related sciatica with a mean duration of 88 +/- 127 days to determine the impact on treatment outcomes of 50 parameters. RESULTS: After complete bed and 2.2 +/- 1.1 epidural glucocorticoid injections during a mean hospital stay of 9.9 +/- 4.3 days, 80% of patients reported either complete or partial pain relief (19% and 61%, respectively). The remaining 20% reported little (9%) or no (11%) change. Surgery was performed in 13% of cases. A tighter straight-leg raising test angle was correlated with treatment failure (P = 0.01). Complete bed rest duration prior to admission was shorter in the 80% of responders (P = 0.036) than in the 20% of nonresponders; in the overall population, patients spent on average 64% +/- 33% of daytime hours in bed. Patient predictions about their own outcomes were unreliable (P = 0.926). Patients who believed strongly that sciatica requires surgical treatment were more likely to be nonresponders (P = 0.06), as were patients with a family history of surgically-treated sciatica (P = 0.055). Outcomes were not correlated with any of the other parameters studied, including sciatica duration (P = 0.13), bedrest duration prior to admission (P = 0.52; mean duration, 18 +/- 29 days), the specialty of the physicians seen, investigations done prior to admission, or a history of sciatica (noted in 65% of cases and treated surgically in 16%). CONCLUSIONS: Eighty percent of patients benefited from their hospital stay. Patient opinions on the merits of nonsurgical and surgical treatments in their own case were not correlated with their own outcomes. A tight straight leg-raising test angle was correlated with a poorer outcome. Neither sciatica duration nor rest duration prior to admission had an influence on outcome. Absence of complete bed rest prior to admission was correlated with a greater likelihood of a therapeutic benefit from the hospital stay.

Adolescent↗

[Tomodensitometric image of the lumbar spine. Study of 150 patients hospitalized for discal sciatica].

OBJECTIVES: There would be some discordance between patient expectations and expert recommendations concerning computed tomography (CT) of the spine for discal disorders. We analyzed patient opinion. PATIENTS AND METHODS: At admission, a 25-item questionnaire was given to 150 patients hospitalized in a rheumatology unit for discal sciatica. Patients were asked to express their expectations concerning the CT exploration. RESULTS: Seventy percent of the patients had already undergone CT explorations requested by a general practitioner (55%) or a specialist (45%), 20% had had two CT explorations and 20% magnetic resonance imaging. Seventy-five percent felt they should have had a CT scan earlier, 85% thought a CT should be performed for back pain of less than one month duration and 96% in case of sciatica for 2 months or more. Patients felt their exploration came "late" because the physician was under financial pressure (52%), had incorrectly appreciated the patient's need (28%) or was incompetent in the matter (22%). Nevertheless, 15% of the patients recognized that the CT scan could be useless and 89% knew that all cases of hernia are not operable. Thirty percent recognized that hernias can go undetected on the CT scan and 78% that they may remain asymptomatic. Finally, 56% of the patients thought that the CT scan would not change their treatment and only 23% expected to undergo surgery sooner because of the CT exploration. DISCUSSION: Several factors would explain what patients expect from CT exploration of the spine: patient understanding that causes other than discal hernia can cause back pain (98%) or sciatic (77%); their fear of having another disorder (56% wanted to be reassured, which would explain in part why 27% hoped the CT would improve pain, 50% wanted to "see" their discal hernia, and 30 wanted to eliminate another cause of their pain); patient distrust of clinical diagnosis which they felt was less pertinent than CT (80% of the patients for generalists and 70% for specialists). Patient expectations did not appear to be limited by fear of irradiation (unrecognized by 90% of the patients) nor the cost of the exploration which was overestimated by 70% of them.

Aged↗

Evidence that preaxial polydactyly in the Doublefoot mutant is due to ectopic Indian Hedgehog signaling.

Patterning of the vertebrate limb along the anterior-posterior axis is controlled by the zone of polarizing activity (ZPA) located at the posterior limb margin. One of the vertebrate Hh family members, Shh, has been shown to be able to mediate the function of the ZPA. Several naturally occurring mouse mutations with the phenotype of preaxial polydactyly exhibit ectopic Shh expression at the anterior limb margin. In this study, we report the molecular characterization of a spontaneous mouse mutation, Doublefoot (Dbf). Dbf is a dominant mutation which maps to chromosome 1. Heterozygous and homozygous embryos display a severe polydactyly with 6 to 8 digits on each limb. We show here that Shh is expressed normally in Dbf mutants. In contrast, a second Hh family member, Indian hedgehog (Ihh) which maps close to Dbf, is ectopically expressed in the distal limb bud. Ectopic Ihh expression in the distal and anterior limb bud results in the ectopic activation of several genes associated with anterior-posterior and proximal-distal patterning (Fgf4, Hoxd13, Bmp2). In addition, specific components in the Hedgehog pathway are either ectopically activated (Ptc, Ptc-2, Gli1) or repressed (Gli2). We propose that misexpression of Ihh, and not a novel Smoothened ligand as recently suggested (Hayes et al., 1998), is responsible for the Dbf phenotype. We consider that Ihh has a similar activity to Shh when expressed in the early Shh-responsive limb bud. To determine whether Dbf maps to the Ihh locus, which is also on chromosome 1, we performed an interspecific backcross. These results demonstrate that Dbf and Ihh are genetically separated by approximately 1.3 centimorgans, suggesting that Dbf mutation may cause an exceptionally long-range disruption of Ihh regulation. Although this leads to ectopic activation of Ihh, normal expression of Ihh in the cartilaginous elements is retained.

Animals↗