[Extrarespiratory manifestations of Mycoplasma pneumoniae: a case report]. / Atteintes extra-respiratoires dues à Mycoplasma pneumoniae : à propos d'un cas.

Extrapulmonary manifestations of Mycoplasma pneumoniae are sometimes severe and may even be life-threatening. A 10-year-old patient was hospitalized due to a flu-like illness lasting 48 h with impaired general condition, after an extended stay in Africa. There was an inflammatory syndrome associated with hyponatremia, but malaria was negative. A triple antibiotic therapy with ceftriaxone, amikacin, and josamycin was started. The progression was marked by the appearance of hypoxemia pneumoniae associated with extrarespiratory manifestations. He initially presented with acute polyradiculoneuropathy, followed by thrombotic events associated with polyserositis, polyarthritis, a maculopapular rash, and then a hemophagocytic syndrome. Bacteriological samples isolated M. pneumoniae in nasopharyngeal secretions with a positive serology. The appropriate antibiotic therapy associated with corticosteroids and immunoglobulins led to clinical improvement and the patient progressed toward complete recovery. The pathogenesis of M. pneumoniae infection remains largely unknown. However, two main categories have been proposed. The lung injury is caused by the invasion of the respiratory epithelium, whereas the extrarespiratory manifestations are probably due to immunological disorders. The knowledge of extrarespiratory manifestations and their pathomechanisms allows further adjustments to therapeutic management.

Nonrigid PET motion compensation in the lower abdomen using simultaneous tagged-MRI and PET imaging.

PURPOSE: We propose a novel approach for PET respiratory motion correction using tagged-MRI and simultaneous PET-MRI acquisitions. METHODS: We use a tagged-MRI acquisition followed by motion tracking in the phase domain to estimate the nonrigid deformation of biological tissues during breathing. In order to accurately estimate motion even in the presence of noise and susceptibility artifacts, we regularize the traditional HARP tracking strategy using a quadratic roughness penalty on neighboring displacement vectors (R-HARP). We then incorporate the motion fields estimated with R-HARP in the system matrix of an MLEM PET reconstruction algorithm formulated both for sinogram and list-mode data representations. This approach allows reconstruction of all detected coincidences in a single image while modeling the effect of motion both in the emission and the attenuation maps. At present, tagged-MRI does not allow estimation of motion in the lungs and our approach is therefore limited to motion correction in soft tissues. Since it is difficult to assess the accuracy of motion correction approaches in vivo, we evaluated the proposed approach in numerical simulations of simultaneous PET-MRI acquisitions using the NCAT phantom. We also assessed its practical feasibility in PET-MRI acquisitions of a small deformable phantom that mimics the complex deformation pattern of a lung that we imaged on a combined PET-MRI brain scanner. RESULTS: Simulations showed that the R-HARP tracking strategy accurately estimated realistic respiratory motion fields for different levels of noise in the tagged-MRI simulation. In simulations of tumors exhibiting increased uptake, contrast estimation was 20% more accurate with motion correction than without. Signal-to-noise ratio (SNR) was more than 100% greater when performing motion-corrected reconstruction which included all counts, compared to when reconstructing only coincidences detected in the first of eight gated frames. These results were confirmed in our proof-of-principle PET-MRI acquisitions, indicating that our motion correction strategy is accurate, practically feasible, and is therefore ready to be tested in vivo. CONCLUSIONS: This work shows that PET motion correction using motion fields measured with tagged-MRI in simultaneous PET-MRI acquisitions can be made practical for clinical application and that doing so has the potential to remove motion blur in whole-body PET studies of the torso.

Influence of HCV genotype 1 subtypes on the virus response to PEG interferon alpha-2a plus ribavirin therapy.

New factors that influence the viral response in HCV non-genotype 2/3 patients must be identified in order to optimize anti-HCV treatment. This multicenter prospective study evaluates the influence of HCV variability and pharmacological parameters on the virological response of these patients to pegylated interferon α2a (peg-IFN-α2a: 180 µg/week) and ribavirin (RBV; 800-1,200 mg/day) for 48 weeks. HCV subtypes were identified by sequencing the NS5B region. Serum RBV and peg-IFN-α2a concentrations were measured at weeks 4 and 12. The 115 patients (67 men; median age = 49, range 31-76) included 64 who had never been treated and 27 co-infected with HIV. The mean baseline HCV RNA was 6.30 ± 0.06 log IU/ml and the HCV genotypes were: G1 (n = 93) with 1a (n = 37) and 1b (n = 50), G4 (n = 20) and G5 (n = 2). Most patients (79/108; 73%) had an early virological response. Independent predictors of an early virological response were interferon naive patients (OR= 2.98, 95% CI: 1.15-7.72) and RBV of >2,200 ng/ml at week 12 (OR = 3.41, 95% CI: 1.31-8.90). Forty of 104 patients (38%) had a sustained virological response. The only independent predictors of a sustained virological response were subtype 1b (OR = 6.82, 95% CI: 1.7-26.8), and HCV RNA <15 IU/ml at week 12 (OR = 25, 95% CI: 6.4-97.6). Thus a serum RBV concentration of >2,200 ng/ml was associated with an early virological response and patients infected with HCV subtype 1b had a better chance of a sustained virological response than did those infected with subtype 1a.

[Transient neonatal thyrotoxicosis: clinical presentation and treatment in 7 cases]. / Complications cliniques et difficultés de prise en charge de l'hyperthyroïdie néonatale transmise.

UNLABELLED: Neonatal thyrotoxicosis is a rare disease. The goal of this study was to analyse main neonatal symptoms, clinical complications and patient's care. MATERIAL AND METHODS: This retrospective study concerned the newborns admitted with neonatal thyrotoxicosis between 1992 and 2004 in the neonatal department of Bordeaux, Toulouse and Pau hospital. RESULTS: Seven of these patients were included in the study. All of the newborns had permanent tachycardia and 3 of them had respiratory failure. Two patients had potentially lethal clinical complications. The first had goitre with tracheal compression. The second developed global heart failure on his 13th day of life. The onset of antithyroid drug treatment was between the 3rd and the 18th day of life. Mean duration of treatment was 50 days. Occurring complications were neutropenia in 3 patients and hypothyroidism in 1 patient. The children were tracked during their first year, and all had normal growth and normal neurological development. CONCLUSION: The main prognostic factor is the early onset of antithyroid treatment. In our study, 2 patients had potentially lethal clinical complications. Adequate care depends on early spotting of high-risk newborn.

Transient adverse effects of an attenuated bluetongue virus vaccine on the quality of ram semen.

This study investigated the effects of the vaccination of rams with a serotype 2 bluetongue virus vaccine on the quality of their semen. One group of 23 rams was vaccinated on days 0 and 47, and 23 rams were left unvaccinated. Samples of blood, serum and semen were collected regularly in order to detect the virus genome, and to compare the quality of the semen from the vaccinated and unvaccinated rams. Segment 10 of the genome of the vaccine strain was detected in the blood of the vaccinated animals by reverse transcriptase-PCR (RT-PCR) on days 7, 13 and 19 after the first vaccination, but no virus was isolated from the RT-PCR-positive blood or from any of the semen samples from the vaccinated animals. There was a significant decrease in the concentration and motility of the spermatozoa and an increase in the proportion of abnormal and dead spermatozoa after the first vaccination; however, after the second vaccination only smaller, non-significant changes were observed. On day 69, the quality of the semen of the vaccinated animals was not significantly different from that of the controls.

[Chromobacterium violaceum peritonitis: case report and literature review]. / Péritonite à Chromobacterium violaceum: observation et revue de la littérature.

We report a case of Chromobacterium violaceum infection and we review the literature for all published cases. C. violaceum grew from a peritoneal fluid of a 47-year-old woman operated on for peritonitis following perforative gastroduodenal ulcer. She was just coming back from a 1-month-holyday in French Guyana, where she might have been in contact with this micro-organism. The patient fully recovered after surgical management associated with antibiotic therapy consisting of ofloxacin plus piperacillin-tazobactam. Among the more than a hundred of published cases of human infections with C. violaceum that we retrieved, there was not any other case of peritonitis.

[Primary hyperparathyroidism revealed by pseudomyopathia]. / Pseudomyopathie révélant une hyperparathyroïdie primitive isolée.

We report the case of an 11-year-old child with delayed development who developed signs of exercise-induced pain in the lower limb muscles after an acute attack of appendicitis. He had difficulty standing up from the sitting position and ascending and descending stairs. The physical examination revealed increased reflex activity in the lower limbs. Initially, blood tests, MRI and EMG were normal. Serum phosphorus and calcium were not assayed. Eight months later, the boy's condition worsened (myopathy gait, hyperlordosis) leading to the possible diagnosis of muscle disease. After muscle biopsy, blood tests revealed hypercalcemia at 3.5 mmol/l (normal 2.2-2.6), hypercalciuria, and hypophosporemia. The diagnosis of primary hyperparathyroidism was confirmed by the abnormal level of parathormone initially (19 ng/ml) and later (156 ng/ml) with hypercalcemia. Medical treatment failed and surgery was performed to remove three and a half parathyroid glands. After removal, blood tests returned to normal in six days and the physical examination in three years. The diagnosis of principal cell hyperplasia was retained at the pathology examination. We found no evidence of hypercalcemia or other endocrinopathy such as multiple endocrine neoplasia (MEN 1 or 2a). Study of the menine gene did not reveal any mutation. Muscle dysfunction suggest possible abnormal phosphocalcium regulation. A normal parathormone level with hypercalcemia reveals inappropriate synthesis and secretion.

Viruses in boar semen: detection and clinical as well as epidemiological consequences regarding disease transmission by artificial insemination.

Many viruses have been reported to be present in boar semen, particularly during the viremic phase of the diseases. Some of them, such foot-and-mouth disease virus, porcine reproductive and respiratory syndrome virus, swine vesicular disease virus, porcine parvovirus, picornaviruses, adenoviruses, enteroviruses, Japanese encephalitis virus, pseudorabies virus, African swine fever virus and reoviruses are of particular importance and accurate monitoring prior to and during the presence of boars in AI stations is essential. Various methods may be used to detect these viruses in the animals, or even directly in batches of semen. Cell culture, ELISA and PCR are the most accurate and widely used. Because of the high risk of dissemination of disease via AI, the absolute goal is to provide pathogen-free semen and this is feasible with the adequate measures that are discussed briefly in this paper.

[Takayasu disease revealed by dorsalgia]. / Dorsalgies révélant une maladie de Takayasu.

UNLABELLED: Takayasu arteritis is an uncommon inflammatory arteritis especially in children. We report a case. CASE REPORT: A 11-year-old boy presented dorsalgia with inflammatory syndrome. One year later, the investigation of an hypertension with asymmetric blood pressure revealed an aortic coarctation and a bilateral renal arteries stenosis leading to Takayasu's arteritis diagnosis. CONCLUSION: Takayasu's arteritis must be evokated in young children in case of associated hypertension and inflammatory syndrome.

[Severe neonatal hyperthyroidism which reveals a maternal Graves' disease]. / Hyperthyroïdie néonatale sévère, révélatrice d'une maladie de Basedow maternelle.

Two of every thousand pregnancies are complicated by Graves' disease. Diagnosis is suggested by maternal disorders (tachycardia, exophthalmia, weight loss.) or fetal disorders (tachycardia, intra-uterine growth retardation, preterm birth.). Due to transfer into the fetal compartment of maternal antibodies which stimulate the fetal thyroid by binding to the thyroid thyrotropin (TSH) receptor, only 1% of children born to these mothers are described as having hyperthyroidism. Neonatal thyrotoxicosis disappears with clearance of the maternal antibodies; clinical signs usually disappear during the first four Months of life. The most frequent neonatal clinical signs of thyrotoxicosis are tachycardia, goiter, hyperexcitability, poor weight gain, hepatosplenomegaly, stare and eyelid retraction. Diagnosis is based on determination of the blood level of triiodothyronine (T3), thyroxine (T4) and TSH. To confirm the nature of hyperthyroidism, thyroid-stimulating immunoglobulins (TSI) should be assayed. The kinetics of TSI provides a guide for therapeutic adaptation and disappearance of TSI is a sign of recovery. Rare cases of familial non-autoimmune hyperthyroidism have been shown to be caused by germline mutation of the thyrotropin receptor. We report a case of severe neonatal hyperthyroidism which led to the diagnosis of maternal Graves' disease.

[Contribution of ultrasonography in the diagnosis of ectopic pregnancy]. / Apport de l'échographie dans le diagnostic de la grossesse extra-utérine.

High-resolution endovaginal sonography has considerably improved ectopic pregnancy imaging. In conjunction with serum hCG measurements, it allows early detection of ectopic pregnancy (EP) and has significantly reduced the morbidity and the mortality of this disease. The major sonographic finding is the uterine vacuity, the diagnosis of ectopic pregnancy is quite sure in case of absence of intra-uterine pregnancy (IUP) associated with serum hCG above 1500 mUi/ml. Conversely, the presence of IUP excludes practically the diagnosis of EP, but IUP must be distinguished from a pseudosac. The visualization of an ectopic sac that contains an embryo or a yolk sac clearly allows the diagnosis of EP, but its sensitivity is only 25%. The most common sonographic finding is a hematosalpinx, which looks like an echogenic adnexal mass, next to the ovary containing the corpus luteum. Color Doppler is useful to enhance ectopic trophoblastic flow, but it is only a complementary technique of endovaginal sonography. Finally, if the first sonography is inconclusive, a follow-up examination must be performed 2 or 4 days later.

[Acute immune epiduritis in a child]. / Epidurite aiguë d'origine immunologique chez un enfant.

Acute epiduritis is an uncommon disease especially in children. We report an unusual case of acute epiduritis in a child, revealed by characteristic clinical signs and Magnetic Resonance Imaging (MRI). Given the absence of identified infectious or tumoral cause, and the ineffectiveness of antimicrobial treatment, a therapeutic test with polyvalent immunoglobulins was implemented. Rapid clinical improvement led to the retrospective diagnosis of probable immunological acute epiduritis.

Single histidine residue in head-group region is sufficient to impart remarkable gene transfection properties to cationic lipids: evidence for histidine-mediated membrane fusion at acidic pH.

Presence of endosome-disrupting multiple histidine functionalities in the molecular architecture of cationic polymers, such as polylysine, has previously been demonstrated to significantly enhance their in vitro gene delivery efficiencies. Towards harnessing improved transfection property through covalent grafting of endosome-disrupting single histidine functionality in the molecular structure of cationic lipids, herein, we report on the design, the synthesis and the transfection efficiency of two novel nonglycerol-based histidylated cationic amphiphiles. We found that L-histidine-(N,N-di-n-hexadecylamine)ethylamide (lipid 1) and L-histidine-(N,N-di-n-hexadecylamine,-N-methyl)ethylamide (lipid 2) in combination with cholesterol gave efficient transfections into various cell lines. The transfection efficiency of Chol/lipid 1 lipoplexes into HepG2 cells was two order of magnitude higher than that of FuGENE(TM)6 and DC-Chol lipoplexes, whereas it was similar into A549, 293T7 and HeLa cells. A better efficiency was obtained with Chol/lipid 2 lipoplexes when using the cytosolic luciferase expression vector (pT7Luc) under the control of the bacterial T7 promoter. Membrane fusion activity measurements using fluorescence resonance energy transfer (FRET) technique showed that the histidine head-groups of Chol/lipid 1 liposomes mediated membrane fusion in the pH range 5-7. In addition, the transgene expression results using the T7Luc expression vector convincingly support the endosome-disrupting role of the presently described mono-histidylated cationic transfection lipids and the release of DNA into the cytosol. We conclude that covalent grafting of a single histidine amino acid residue to suitable twin-chain hydrophobic compounds is able to impart remarkable transfection properties on the resulting mono-histidylated cationic amphiphile, presumably via the endosome-disrupting characteristics of the histidine functionalities.

Participation of acetaldehyde dehydrogenases in ethanol and pyruvate metabolism of the yeast Saccharomyces cerevisiae.

This work was undertaken to clarify the role of acetaldehyde dehydrogenases in Saccharomyces cerevisiae metabolism during growth on respiratory substrates. Until now, there has been little agreement concerning the ability of mutants deleted in gene ALD4, encoding mitochondrial acetaldehyde dehydrogenase, to grow on ethanol. Therefore we constructed mutants in two parental strains (YPH499 and W303-1a). Some differences appeared in the growth characteristics of mutants obtained from these two parental strains. For these experiments we used ethanol, pyruvate or lactate as substrates. Mitochondria can oxidize lactate into pyruvate using an ATP synthesis-coupled pathway. The ald4Delta mutant derived from the YPH499 strain failed to grow on ethanol, but growth was possible for the ald4Delta mutant derived from the W303-1a strain. The co-disruption of ALD4 and PDA1 (encoding subunit E1alpha of pyruvate dehydrogenase) prevented the growth on pyruvate for both strains but prevented growth on lactate only in the double mutant derived from the YPH499 strain, indicating that the mutation effects are strain-dependent. To understand these differences, we measured the enzyme content of these different strains. We found the following: (a) the activity of cytosolic acetaldehyde dehydrogenase in YPH499 was relatively low compared to the W303-1a strain; (b) it was possible to restore the growth of the mutant derived from YPH499 either by addition of acetate in the media or by introduction into this mutant of a multicopy plasmid carrying the ALD6 gene encoding cytosolic acetaldehyde dehydrogenase. Therefore, the lack of growth of the mutant derived from the YPH499 strain seemed to be related to the low activity of acetaldehyde oxidation. Therefore, when cultured on ethanol, the cytosolic acetaldehyde dehydrogenase can partially compensate for the lack of mitochondrial acetaldehyde dehydrogenase only when the activity of the cytosolic enzyme is sufficient. However, when cultured on pyruvate and in the absence of pyruvate dehydrogenase, the cytosolic acetaldehyde dehydrogenase cannot compensate for the lack of the mitochondrial enzyme because the mitochondrial form produces intramitochondrial NADH and consequently ATP through oxidative phosphorylation.

Cyclofunctionalization and free-radical-based hydrogen-transfer reactions. An iterative reaction sequence applied to the synthesis of the C(7)-C(16) subunit of zincophorin.

The strategy considered herein features an iodocyclofunctionalization/hydrogen-transfer reaction sequence for the elaboration of propionate motifs. Proceeding with excellent yield and diastereoselectivity, the synthetic sequence proposed gives access to the anti-anti dipropionate motif when the reduction step is performed under the control of the exocyclic effect. The tandem sequence is applied successfully to the synthesis of the C(7)-C(16) subunit of zincophorin, and iteration of the process gives the desired anti-anti-anti-anti polypropionate stereopentad. Modifications of the reaction sequence--including phenylselenocyclofunctionalization, carbonate hydrolysis, and chelation-controlled radical reduction reactions--lead to the formation of the anti-syn dipropionate motif with remarkable diastereocontrol.