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Biomedical subjects

J Caron

Publications and source records attributed to J Caron.

At least 19 recordsLinked to original sources

[Helical tomotherapy: general methodology for clinical and dosimetric evaluation (national French project)].

The methodology and choice of criteria and indexes used for a common evaluation of helical tomotherapy by 3 French centres are described. After a selection of clinical indications and definition of the general purpose are successively described the criteria and index selected for: 1) description of volumes and adaptation for on board imaging; 2) dose prescription and constraints related to IMRT; 3) intercomparaison of volumes and doses and potential dosimetric gain with this new equipment.

France↗

[How to interprete hypercalcitoninemia?].

PURPOSE: Today, calcitonin assay is used for the diagnosis of thyroid medullary cancer in the context of nodular thyroid disease. Calcitonin is an excellent marker of thyroid medullary cancer but some hypercalcitoninemia can also be related to other diseases, such as renal failure, endocrine tumors other than thyroid medullary cancer and sometimes to C cell hyperplasia, which is a not well-defined situation. Recent studies contributed to define calcitoninemia thresholds, which guide decision and avoid excessive invasive treatment. CURRENT KNOWLEDGE AND KEY POINTS: After a brief reminder of physiological role of calcitonin and assays, the difficulties encountered in interpreting hypercalcitoninemia and its potential causes other than thyroid medullary cancer are addressed. Recent studies, on large series, now allow a better knowledge of specificity and sensitivity of calcitonin measurement in patients with nodular thyroid disease and a well-argued management. FUTURE PROSPECTS AND PROJECTS: In the future, calcitonin dosage will be ordered even more frequently, as some authors recommend it for the diagnosis of thyroid nodule. It is up to us to know how to use this remarkable marker, by considering all possible situations of benign hypercalcitoninemia and reserving aggressive treatments for patients who really need them.

Adult↗

Mapping of interactions and mouse congenic strains identified novel epistatic QTLs controlling the persistence of Salmonella Enteritidis in mice.

The host response to infection in humans is multifactorial and involves the complex interaction between two genomes (the host and the pathogen) and the environment. Using an experimental mouse model of chronic infection, we have previously identified the individual effect of three significant and one suggestive quantitative trait loci (QTLs) (Ses1, Ses2, Ses3 and Ses1.1) on Salmonella Enteritidis persistence in target organs of 129S6/SvEvTac mice. Congenic strain construction was performed by transferring each of these QTLs from C57BL/6J onto the 129S6/SvEvTac background, and phenotypic analysis confirmed that Ses1 and Ses1.1 contribute to bacterial clearance. Additional QTLs regulating Salmonella carriage in 129S6/SvEvTac mice were identified using a two-locus epistasis QTL linkage mapping approach conducted separately in females and males. The epistatic model for females included the individual effect of Ses3 and two significant interactions (Ses1-D7Mit267 and Ses1-DXMit48) accounting for 47% of the total phenotypic variance. The model for males included the individual effect of Ses1.1, three interactions (Ses1-D9Mit218, D2Mit197-D4Mit2 and D3Mit256-D13Mit36) and explained 47% of the phenotypic variance. Our results suggest that the oligogenic nature of Salmonella persistence and epistasis are important constituents of the genetic architecture of the host response to chronic Salmonella infection.

Animals↗

[Comparison of intensity-modulated postoperative radiotherapy with conventional postoperative conformal radiotherapy for retroperitoneal sarcoma].

External postoperative radiation therapy for retroperitoneal sarcoma is an example of treatment using large fields for complex shaped volumes of irradiation. Prescribed dose is limited by tolerance of adjacent organs at risk (OAR). From a recent case treated by conventional conformal radiotherapy (3D-CRT), we evaluate the benefit of five theoretical IMRT plans. Criteria used are calculated from DVH related to delineated PTV and OAR. IMRT should permit to enhance the prescribed dose without increasing dose in the OAR (especially residual kidney, spinal cord and small bowel). This theoretical study show the feasibility of a dose escalation from a treatment dose of 45 Gy delivered by 3D-CRT up to a planning dose of 54 Gy calculated by IMRT with: for the PTV: an improvement of the dose homogeneity about 5% (range 2-6%) and moreover the coverage factor (CF) about 13% (range 9-16%); for the OAR: an improvement of the protection factor (PF) about 20% (range 11-24%); and thus an improved conformity index (CI = CF x PF) about 25% (range 15-32%).

Feasibility Studies↗

[Flaccid tetraplegia following anti-tetanus vaccination].

INTRODUCTION: Anti-tetanus vaccination is considered to be very safe. However complications such as mononevritis, multinevritis or even polyradiculonevritis can be encountered. OBSERVATION: An 85-year-old man was admitted to our unit after a traffic accident caused by stroke. Seventy-two hours later the patient developed tetraplegia within a few hours, caused by neuropathy secondary to anti-tetanus vaccination. DISCUSSION: In this elderly patient, the rapid onset and severe presentation of the tetraplegia as well as the past history of normal vaccination and the axonal form of the neuropathy could have led to a misdiagnosis of neuropathy after booster anti-tetanus vaccination. We first ruled out other possible diagnoses and then reviewed the possible mechanisms of neurological complications of vaccinations. These complications are probably underestimated in elderly hospitalized patients who receive a booster shot in the emergency department. CONCLUSION: This report illustrates the importance of reconsidering the benefit/risk relationship of anti-tetanos vaccination.

Accidents, Traffic↗

[Non infectious skin conditions associated with diabetes mellitus: a prospective study of 308 cases].

INTRODUCTION: Non-infectious dermatoses during diabetes appear frequent if one refers to some of the studies in the literature that have attempted to assess its prevalence. PATIENTS AND METHODS: From November 2000 to November 2001, 308 randomly selected, hospitalized, diabetic patients were examined. The data were collected prospectively and systematically in a pre-established questionnaire. Statistical analysis included a descriptive and univariate analysis. RESULTS: 206/308 diabetics (67 p. 100) exhibited at least one non-infectious dermatitis, the most frequent of which was cutaneous xerosis (39 p. 100), diabetic dermopathy (24 p. 100), facial erythrosis (24 p. 100), purpural and pigmented capillaritis of the legs (20 p. 100), xanthochromia (12 p. 100) pseudo-scleroderma (8 p. 100) and acanthosis nigricans (7 p. 100). The non-infectious dermatoses were globally more frequent in type II diabetic patients exhibiting at least one microvascular complication. DISCUSSION: This study is the first French prospective work on the subject. We found a prevalence of non-infectious dermatoses during diabetes close to that of the major studies in the literature. Some of these dermatoses are markers of macrovascular (acanthosis nigricans, purpural and pigmented capillarity) or microvascular (xerosis, acanthosis nigricans, purpural and pigmented capillarity, Dupuytren's disease) complications for type II diabetes or are markers of auto-immunity (alopecia areata, vitiligo) for type I.

Adult↗

Identification of genetic loci controlling bacterial clearance in experimental Salmonella enteritidis infection: an unexpected role of Nramp1 (Slc11a1) in the persistence of infection in mice.

The Gram-negative bacteria, Salmonella, cause a broad spectrum of clinical diseases in both animals and humans ranging from asymptomatic carriage to life-threatening sepsis. We have developed a model to study the contribution of genetic factors to the susceptibility of 129sv and C57BL/6J inbred mice to Salmonella enteritidis during the late phase of infection. C57BL/6J mice were able to eliminate completely sublethal inoculums of S. enteritidis from their reticuloendothelial system, whereas 129sv mice could not even after 60 days post inoculation. A genome scan performed on 302 (C57BL/6J x 129sv) F2 progeny identified three dominant loci (designated Ses1 to Ses3) that are associated with disease susceptibility in 129sv mice. Two highly significant linkages were identified on chromosomes 1 (Ses1) and 7 (Ses2) with respective LOD scores of 9.9 (P = 1.4 x 10(-11)) at D1Mcg5 and 4.0 (P = 1.9 x 10(-5)) at D7Mit62. One highly suggestive QTL was located on chromosomes15 (Ses3) with a LOD score 3.4 (P = 1.2 x 10(-4)). The estimated effects of Ses1, Ses2 and Ses3 on the bacterial clearance were greater in females. Using a model of three loci, with interaction between Ses1 and Ses2 and sex as a covariate, the three QTLs explained 32% of the phenotypic variance. The candidacy of Nramp1 as the gene for Ses1 was evaluated using mice carrying a null allele at Nramp1 (129sv-Nramp1(tm1Mcg)). These mice have a significantly lower spleen bacterial load compared to the wild-type 129sv mice, strongly suggesting the involvement of Nramp1 in controlling S. enteritidis clearance during the late phase of infection.

Animals↗

[Celecoxib induced toxiderma with positive patch-test].

INTRODUCTION: Celecoxib (Celebrex(R)) is a new generation non-steroidal anti-inflammatory drug, recently introduced in France. We report a maculopapular rash due to this drug with positive patch-tests. CASE REPORT: A forty year-old man received with 3 tablets/day of celecoxib for intercostal pain. Nine days after initiation of treatment a maculopapular rash appeared. At the end of treatment, the eruption persisted for two days, then rapidly improved within one week. Six weeks later, patch-tests with celecoxib diluted at 20 p. 100 in petrolatum were positive at 48 hours. DISCUSSION: Cutaneous reactions due to celecoxib are rare. In our case report, the delay, clinical aspect, improvement on withdrawal of treatment and positive patch test all emphasize the imputability of celecoxib. We wish to underline the possible cutaneous reactions with this new non-steroidal anti-inflammatory drug.

Adult↗

[Unsuccessful surgery of Cushing's disease. Role and efficacy of fractionated stereotactic radiotherapy].

BACKGROUND AND PURPOSE: To optimize and reduce the toxicity of pituitary adenoma irradiation, we evaluated the feasibility and effectiveness of fractionated stereotactic radiotherapy (FSR) in 51 patients with functional adenoma; 12 of them had Cushing's disease. PATIENTS AND METHODS: Eleven females and one male, median age: 49 years, 8 of them relapsed and 4 had persistent hormonal secretion after surgery. The delivered dose was 50 grays (Gy) (5 x 1.8 Gy/week) using 5 convergent micro-beams scanning in arc therapy mode. The median planned target volume (PTV) receiving 90 to 100% of the total dose was 2,1 cm(3). We used relocatable non-invasive stereotactic device Brain Lab, and adapted Linac for stereotactic radiotherapy. RESULTS: Nine out of twelve patients (75%) presented with complete remission after a median time of 29 months, 3/12 patients with partial remission. Actuarial probability to have hormonal persistent secretion was 88% at on year, 44% from 3 to 5 years, 22% at 7 years, and 11% to 0% after 7 years. The 12-corticotroph adenomas were significantly (p=0.007) more radiosensitive than 39 non-corticotroph adenomas. Toxicity was significantly lower for corticotrope adenoma, with no radio-induced pituitary deficiency and no neurological or optic injury. CONCLUSIONS: Combined surgery and FSR appears to be safe and effective for treatment of pituitary adenomas. However, long-term follow-up is required to determine the impact in terms of tumor response and hormone deficiency. The focused treated volume obtained by FSR seems more suitable for these benign tumours than standard radiotherapy. In addition to this conformal approach, the use of standard fractionation reduced the risk of severe damage to the optic chiasma, which is sometimes observed after radiosurgery and is inherent in single fraction radiotherapy.

Adenoma↗

Fatal aplastic anaemia associated with clopidogrel.

Clopidogrel, an inhibitor of platelet aggregation, was initially thought to be free of the side-effects of ticlopidine. We describe a man who developed aplastic anaemia after 5 months of treatment with clopidogrel. There were no other plausible causes. We suggest that his fatal aplastic anaemia might have been induced by clopidogrel.

Aged↗

Analysis of the direct cost of adverse drug reactions in hospitalised patients.

The hospitalised patients in a cardiological hospital (Lille, France) over an 18-month period were subjected to a prospective high-intensity adverse drug reaction (ADR) monitoring in order to assess the additional financial resource utilisation associated with ADRs and analyse the distribution of excess of cost according to ADR nature and therapeutic classes. Over 18 months, among the 16,916 hospitalised patients, 371 verified ADRs detected by self-report stimulated by a special unit of nurses and pharmacologists occurred in 336 patients with an overall ADR rate of 2.2%. This rate increased with age. The most common reactions were cutaneous events (24%), cardiovascular events (21%), metabolic disorders (12%), coagulation disorders (10%) and nervous system impairment (10%). The most common drug classes involved were cardiovascular agents (36%), contrast media (20%), drugs affecting blood clotting (13%) and anti-infectives (14%). Increased ADR-induced costs result especially from prolongation of length of stay and cost increase was evaluated at Euro 4150 per ADR. Among the 371 ADRs, 134 ADRs, which were significantly more severe, induced a prolongation of length of stay. Renal insufficiency and cardiovascular events were significantly over-represented in this sub-group. The most common ADR-inducing drugs associated with a prolongation of length of stay are cardiovascular agents and drugs affecting blood clotting. In contrast, cutaneous ADRs were significantly over-represented in the group of ADRs without prolongation of length of stay. The severity and substantial costs of ADRs in hospital justify investments to prevent these events. Nevertheless, only a portion of ADRs induces cost increases, suggesting that prevention efforts should focus on this limited category of ADRs.

Adult↗

Species-specific monoclonal antibodies to Escherichia coli-expressed p36 cytosolic protein of Mycoplasma hyopneumoniae.

The p36 protein of Mycoplasma hyopneumoniae is a cytosolic protein carrying species-specific antigenic determinants. Based on the genomic sequence of the reference strain ATCC 25934, primers were designed for PCR amplification of the p36-encoding gene (948 bp). These primers were shown to be specific to M. hyopneumoniae since no DNA amplicons could be obtained with other mycoplasma species and pathogenic bacteria that commonly colonize the porcine respiratory tract. The amplified p36 gene was subcloned into the pGEX-4T-1 vector to be expressed in Escherichia coli as a fusion protein with glutathione S-transferase (GST). The GST-p36 recombinant fusion protein was purified by affinity chromatography and cut by thrombin, and the enriched p36 protein was used to immunize female BALB/c mice for the production of anti-p36 monoclonal antibodies (MAbs). The polypeptide specificity of the nine MAbs obtained was confirmed by Western immunoblotting with cell lysates prepared from the homologous strain. Cross-reactivity studies of the anti-p36 MAbs towards two other M. hyopneumoniae reference strains (ATCC 25095 and J strains) and Quebec field strains that had been isolated in culture suggested that these anti-p36 MAbs were directed against a highly conserved epitope, or closely located epitopes, of the p36 protein. No reactivity was demonstrated against other mycoplasma species tested. Clinical signs and lesions suggestive of enzootic pneumonia were reproduced in specific-pathogen-free pigs infected experimentally with a virulent Quebec field strain (IAF-DM9827) of M. hyopneumoniae. The bacteria could be recovered from lung homogenates of pigs that were killed after the 3-week observation period by both PCR and cultivation procedures. Furthermore, the anti-p36 MAbs permitted effective detection by indirect immunofluorescence of M. hyopneumoniae in frozen lung sections from experimentally infected pigs. However, attempts to use the recombinant p36 protein as an antigen in an indirect enzyme-linked immunosorbent assay for the detection of antibodies in sera from convalescent pigs showed no correlation with clinical and pathological findings.

Animals↗

Diagnosis and differentiation of Mycoplasma hyopneumoniae and Mycoplasma hyorhinis infections in pigs by PCR amplification of the p36 and p46 genes.

The genome of Mycoplasma hyopneumoniae encodes several immunodominant proteins, including a cytosolic protein (p36), three membranous proteins (p46, p65, and p74), and an adhesin (p97). Cross-reactions with M. flocculare and M. hyorhinis reduce the specificity of conventional serological detection methods. However, certain antigenic determinants of the p36 and p46 proteins have been shown to be specific for M. hyopneumoniae. In the present study, pairs of oligonucleotide primers were designed to permit PCR amplification of entire p36 and p46 genes and of internal fragments of these genes. Specific amplicons could be obtained with as low as 0.5 to 50 pg of extracted chromosomal DNA. No amplification product was obtained when testing p36 and p46 primer pairs with genomic DNA or RNA from other mycoplasma species, bacteria, and viruses commonly associated with respiratory diseases in pigs. By using the single p36-PCR method, a positive reaction was demonstrated in 100% (30 of 30) of lungs from pigs that developed typical lesions associated with an M. hyopneumoniae infection, and no false-positive results were detected when 62 apparently normal lungs were tested. On the other hand, with the single p46-PCR method a sensitivity of 86.6% (26 of 30) and a specificity of 96.7% (60 of 62) were obtained in comparison with the necropsy findings. A mixed infection with M. hyorhinis was diagnosed in 13.3% (4 of 30) of the cases by using species-specific primers for the heterologous p37 gene. The sensitivity of the single p36-PCR method for the detection of M. hyopneumoniae, when tested on tracheobronchial swabs, was 100% (20 positive samples), with a specificity of 93.3% (14 of 15 negative samples), compared to the necropsy findings. Both expected amplicons were obtained with 86.6% (26 of 30) positive lungs when p36 and p46 primers were used simultaneously (multiplex PCR) to further increase the specificity of the PCR assay.

Animals↗