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Biomedical subjects

P Coulon

Publications and source records attributed to P Coulon.

At least 19 recordsLinked to original sources

Great vessel management for endovascular exclusion of aortic arch aneurysms and dissections.

OBJECTIVES: To evaluate a recent approach for the endovascular repair of thoracic aortic aneurysms and dissections involving the aortic arch in high risk patients (HRP). METHODS: Amongst 102 thoracic aortic aneurysms and dissections, we treated 25 patients for aortic arch endovascular exclusion after transposition of the great vessels, of which 14 (56%) had thoracic aortic arch aneurysms and 11 type A and B chronic aortic dissections. Total transpositions were done in 15 cases (60%) and hemi-arch transpositions in 10. We then used Talent, Excluder and Zenith endografts in 12, seven and six cases, respectively. RESULTS: Surgical transpositions were complicated by one minor stroke, which worsened to a major stroke (4%) after endovascular exclusion. After endovascular exclusions, two patients (8%) died from catheterization related complications. One patient had a delayed minor stroke (4%). The successful exclusion rate was 92%. During follow-up (15+/-5.8 months), one patient (4%) developed unilateral limb palsy, successfully treated by CSF drainage. The late exclusion rate remained 92%. No stent-related complications were seen. CONCLUSIONS: Transposition of supra-aortic vessels allows the endovascular exclusion of the aortic arch in HRP. Aortic endografting after surgical transposition proved to be feasible and offers good mid-term results. Specialized surgical centers with both endovascular and surgical expertise are required to treat these patients.

Aged↗

Novel technique: staged hybrid surgical and endovascular treatment of acute Type A aortic dissections with aortic arch involvement.

AIM: The standard approach for treating acute Type A aortic dissections (TAD) is replacement of the ascending aorta utilizing hypothermic circulatory arrest (HCA), which is associated with significant morbidity and frequently leaves a residual aortic arch dissection. We describe a staged surgical and endovascular technique of ascending aorta replacement and simultaneous aorto-innominate artery bypass without HCA, followed 4 weeks later by carotid-carotid bypass and endovascular exclusion of the remaining arch dissection with a thoracic endograft. METHODS: From December 2004 to December 2005, 5 consecutive patients (mean age 58 +/- 6.9 years) with TADs underwent the staged procedure. All patients underwent replacement of the ascending aorta and aorto-innominate bypass. Two patients subsequently underwent the second endovascular stage. In one patient the aortic false lumen completely thrombosed following the first surgical stage and two patients are currently awaiting the endovascular stage. RESULTS: There were no major adverse events (death, cerebrovascular accident or paraplegia) following the first surgical stage. One patient suffered a transient minor stroke. The 2 patients who underwent the second endovascular stage showed no immediate adverse events. Postoperative CT scans have demonstrated that the false channel was excluded from the aortic arch down to the distal end of the endograft in the descending aorta in each case, but became patent further downstream. CONCLUSIONS: This procedure appears safe and feasible. It may allow for a more definitive treatment of TADs than the standard surgical approach. It can be adapted by low volume centers, surgeons untrained in aortic arch repair, and in high risk patients.

Acute Disease↗

Great vessels transposition and aortic arch exclusion.

AIM: We describe our experience in endovascular repair of Thoracic Aortic Aneurysms and Dissections (TAAD) involving the aortic arch in high risk patients (HRP). METHODS: Twenty-nine patients presented with TAAD involving the aortic arch and were treated by endovascular exclusion. Pathologies were as follows: atherosclerotic aneurysms of the descending thoracic aorta in 15 cases, acute Stanford type A dissections in 6 cases, Stanford type B dissections in 7 cases (1 acute), and 1 false aneurysm of the ascending aorta. Total-arch transpositions of all supra-aortic vessels (aortic debranching) to the ascending aorta were done in 11 cases throught median sternotomy. We performed carotido-carotid bypass (hemi-arch transposition) in 16 patients by cervicotomy. Secondary to surgical transpositions, we placed endovascular stentgrafts in all but 2 patients for final exclusion, the 2 remaining being planned for later exclusion. The Talent, Excluder, TAG and Zenith endografts were used in 12, 3, 1 and 4 cases respectively. Banding technique was associated in some cases. RESULTS: All surgical transpositions were successful although 1 led to a minor stroke (1/29=3.5%), which worsened to major stroke after endovascular exclusion. Endovascular procedures were performed in all but one case (26/27=96.3%). Two patients (2/26=7.7%) died from catheterization related complications after endovascular exclusion (iliac rupture and left ventricle perforation). One patient had a delayed minor stroke (1/26=3.8%). Recirculation was found in 13.3% (2/15) of aneurysms and 27.3% of thoracic false channels. During a mean follow-up of 15.7 months (13 days to 45.5 months), 1 patient (1/26=3.8%) who had preoperative chronic pulmonary failure died at 6 months from respiratory worsening. We observed one case (3.8%) of unilateral limb palsy unrelated to cerebral ischemia, which we successfully treated by cerebrospinal fluid (CSF) drainage. No stent-related complication was seen. One new type 1 endoleak appeared at 12 months on an aneurysm, which resolved after stentgraft extension. Three thoracic dissection false channels remained patent during follow-up, of which one was retrograde originating distally in the descending aorta. CONCLUSIONS: Secondary endovascular exclusion of thoracic aortic diseases involving the arch in HRP is made feasible thanks to the preliminary aortic debranching. Total-arch transposition may be of greater interest in case of proximal neck length uncertainty and potential embolization from the aortic arch. Mid-term results are good although patients must be followed carefully to detect aortic recirculation and enlargement.

Aged↗

Phox2a gene, A6 neurons, and noradrenaline are essential for development of normal respiratory rhythm in mice.

Although respiration is vital to the survival of all mammals from the moment of birth, little is known about the genetic factors controlling the prenatal maturation of this physiological process. Here we investigated the role of the Phox2a gene that encodes for a homeodomain protein involved in the generation of noradrenergic A6 neurons in the maturation of the respiratory network. First, comparisons of the respiratory activity of fetuses delivered surgically from heterozygous Phox2a pregnant mice on gestational day 18 showed that the mutants had impaired in vivo ventilation, in vitro respiratory-like activity, and in vitro respiratory responses to central hypoxia and noradrenaline. Second, pharmacological studies on wild-type neonates showed that endogenous noradrenaline released from pontine A6 neurons potentiates rhythmic respiratory activity via alpha1 medullary adrenoceptors. Third, transynaptic tracing experiments in which rabies virus was injected into the diaphragm confirmed that A6 neurons were connected to the neonatal respiratory network. Fourth, blocking the alpha1 adrenoceptors in wild-type dams during late gestation with daily injections of the alpha1 adrenoceptor antagonist prazosin induced in vivo and in vitro neonatal respiratory deficits similar to those observed in Phox2a mutants. These results suggest that noradrenaline, A6 neurons, and the Phox2a gene, which is crucial for the generation of A6 neurons, are essential for development of normal respiratory rhythm in neonatal mice. Metabolic noradrenaline disorders occurring during gestation therefore may induce neonatal respiratory deficits, in agreement with the catecholamine anomalies reported in victims of sudden infant death syndrome.

Animals↗

Altered respiratory activity and respiratory regulations in adult monoamine oxidase A-deficient mice.

The abnormal metabolism of serotonin during the perinatal period alters respiratory network maturation at birth as revealed by comparing the monoamine oxidase A-deficient transgenic (Tg8) with the control (C3H) mice (Bou-Flores et al., 2000). To know whether these alterations occur only transiently or induce persistent respiratory dysfunction during adulthood, we studied the respiratory activity and regulations in adult C3H and Tg8 mice. First, plethysmographic and pneumotachographic analyses of breathing patterns revealed weaker tidal volumes and shorter inspiratory durations in Tg8 than in C3H mice. Second, electrophysiological studies showed that the firing activity of inspiratory medullary neurons and phrenic motoneurons is higher in Tg8 mice and that of the intercostal motoneurons in C3H mice. Third, histological studies indicated abnormally large cell bodies of Tg8 intercostal but not phrenic motoneurons. Finally, respiratory responses to hypoxia and lung inflation are weaker in Tg8 than in C3H mice. dl-p-chlorophenyl-alanine treatments applied to Tg8 mice depress the high serotonin level present during adulthood; the treated mice recover normal respiratory responses to both hypoxia and lung inflation, but their breathing parameters are not significantly affected. Therefore in Tg8 mice the high serotonin level occurring during the perinatal period alters respiratory network maturation and produces a permanent respiratory dysfunction, whereas the high serotonin level present in adults alters the respiratory regulatory processes. In conclusion, the metabolism of serotonin plays a crucial role in the maturation of the respiratory network and in both the respiratory activity and the respiratory regulations.

Animals↗

Optimization of a new scintillation gas detector used to localize electrons emitted by 99mTc.

UNLABELLED: We have developed a scintillation gas detector to localize electrons emitted by 99mTc. This type of detector allows direct quantification of images and so provides a clear advantage over autoradiographic film. We have optimized the device to give an image spatial resolution that closely approximates that of typical autoradiographic film. To improve this resolution, it was necessary to select only low-energy electrons (2 and 15 keV) and to devise novel detection and localization techniques for the ionizing particles. METHODS: A parallel-plate proportional avalanche chamber is subject to a uniform electrical field and amplifies the number of released electrons through collisions of ionizing particles in the gas mixture. Light emitted by the gas scintillator during the avalanche process is collected by a highly intensified charge coupled device camera. The centroid of each resulting light distribution is calculated, resulting in a quantitative mapping of the sample's activity. Insertion of the sample within the gas volume improves the efficiency and so provides a method that is both very sensitive and linear. RESULTS: We have shown that in a parallel-plate structure, the application of a high electrical field to the surface of the sample and the selection of appropriate light spots, according to their morphology, can overcome localization errors due to the particles' trajectories. We have obtained a resolution of the order of 30 microm, using electrons from 99mTc. CONCLUSION: This detection technique allows considerable improvement in image resolution. This "electron camera" is a serious rival to existing autoradiographic techniques, because it provides certain other advantages, including direct quantification, linearity, high dynamic range and low noise levels. Thus, new perspectives are made available in quantitative double tracer autoradiography, because electrons can be selected for imaging as a function of their energy.

Animals↗

Influence of acetylcholinesterase on embryonic spinal rat motoneurones growth in culture: a quantitative morphometric study.

Rat spinal motoneurones sampled at day embryonic 15 were purified using a Nycodenz gradient and cultured in defined medium, during 7 days, on glass coverslips coated with poly-L-lysine and laminine. Purified acetylcholinesterase (AChE), ecothiopate, BW 284C51 and fasciculin II, inhibitors of either the catalytic or peripheral site of AChE, were added to the defined medium. Morphological changes of spinal motoneurones were measured using a statistical quantitative morphometric method, allowing the determination of various parameters such as the number of neurites and bifurcations, the length of neurites, the surface and spreading index. Presence of AChE in the medium (4 units/mL) increases the surface and the total length of neurites and axons without any change in the spreading index. When spinal motoneurones were cultured on AChE coated substrate, neurones rapidly migrate and form clusters. Addition of ecothiopate (10(-6) M) in the medium, which selectively blocks the catalytic site of AChE, leads to a slight increase in the number of primary neurite and a decrease of the spreading index during the three first days in culture. BW 284C51 (10(-5) M) which blocks the catalytic site but also affect the peripheral one, significantly reduces the number of primary neurites and increases the number of bifurcations. Fasciculin II, a potent blocker (10(-9)M) of the AChE peripheral site induces a decrease of both primary neurites and bifurcations with a significant increase of the length and growth velocity of the axon, giving a drastic enhancement of the spreading index. These phenomena are discussed in terms of catalytic and non-catalytic function of AChE, including the involvement of the enzyme in adhesive processes, occurring during growth and differentiation of spinal motoneurones.

Acetylcholinesterase↗

An avirulent mutant of rabies virus is unable to infect motoneurons in vivo and in vitro.

An antigenic double mutant of rabies virus (challenge virus standard [CVS] strain) was selected by successive use of two neutralizing antiglycoprotein monoclonal antibodies, both specific for antigenic site III. This mutant differed from the original virus strain by two amino acid substitutions in the ectodomain of the glycoprotein. The lysine in position 330 and the arginine in position 333 were replaced by asparagine and methionine, respectively. This double mutant was not pathogenic for adult mice. When injected intramuscularly into the forelimbs of adult mice, this virus could not penetrate the nervous system, either by the motor or by the sensory route, while respective single mutants infected motoneurons in the spinal cord and sensory neurons in the dorsal root ganglia. In vitro experiments showed that the double mutant was able to infect BHK cells, neuroblastoma cells, and freshly prepared embryonic motoneurons, albeit with a lower efficiency than the CVS strain. Upon further incubation at 37 degrees C, the motoneurons became resistant to infection by the mutant while remaining permissive to CVS infection. These results suggest that rabies virus uses different types of receptors: a molecule which is ubiquitously expressed at the surface of continuous cell lines and which is recognized by both CVS and the double mutant and a neuron-specific molecule which is not recognized by the double mutant.

Amino Acid Sequence↗

Outcome of patients treated for tuberculosis in Vaud County, Switzerland.

SETTING: The outcome of tuberculosis treatment is often not assessed in low-incidence countries such as Switzerland. In economically developed countries, private practitioners do not have the final responsibility for ensuring the completion of adequate tuberculosis treatment, and public health officers have little or no legal means of intervening if they are not specifically requested to do so. Furthermore, the reluctance of private practitioners to follow official guidelines may be an obstacle to the implementation of a regular surveillance policy. OBJECTIVE: To assess the results of treatment in patients with culture-positive pulmonary tuberculosis and to identify the risk factors for non-adherence to treatment. DESIGN: Retrospective study of all cases notified between 1988 and 1992 in Vaud County, and mainly treated by independent practitioners. RESULTS: Among 133 patients notified with culture-positive pulmonary tuberculosis, complete information about treatment outcome was available for 120. Treatment success (cure or completed adequate treatment) was observed in 84 patients (70%), 17 died (14%) and 19 (16%) were considered as defaulters. The default rate was higher among immigrants, alcoholics, intravenous drug users and male patients. Among non-adherent patients, 4/19 (21%) relapsed within 3 years, compared with 3/84 (4%) among adherent patients. CONCLUSION: The outcome of treatment in this group of patients does not correspond to the expected standards: the treatment completion rate was too low, and the default rate was too high. Better education of medical staff and health-care workers, use of directly-observed treatment, and regular surveillance of treatment outcome will be necessary to improve the results.

Adult↗

Monoclonal antibodies which recognize the acidic configuration of the rabies glycoprotein at the surface of the virion can be neutralizing.

Around 15% of our anti-glycoprotein monoclonal antibodies (MAbs) failed to neutralize the infectivity of the rabies virus during a 1-hr incubation at room temperature. In previous studies, we have demonstrated that it is possible to induce a massive conformational change of the glycoprotein population by incubating the virus at acidic pH. The conformational change is reversible and consequently viral infectivity is not affected by transient exposure at acidic pH. The proportion of glycoproteins in acidic or neutral configuration depends on the pH which means that even at neutral pH some glycoproteins transiently adopt the acidic configuration and vice versa. Here we report that some of our nonneutralizing MAbs recognize the acidic form of the glycoprotein at the virion surface. After incubation of the virus at pH 6.4, most glycoproteins are in the acidic configuration. Further 1-hr incubation with these MAbs at the same pH resulted in more immunoglobulins being attached to the virus and consequently neutralization was induced. It was also possible to induce neutralization with the same MAbs by incubation at neutral pH for a longer period or at a higher temperature. Mutants resistant to neutralization by these MAbs could be selected. Mutations confering resistance to neutralization were not localized in previously described antigenic sites and did not modify these sites at distance. They had no effect on the pathogenic power of the virus. Either they are situated in the epitope or they modify the epitope, so that it is no longer recognized by the antibody on the acidic configuration of the protein. Alternatively, these mutations may stabilize the protein in its neutral configuration. In addition, these experiments confirm our previous finding that neutralization requires the fixation of a large number of immunoglobulins on the virus, irrespective of the region of the protein recognized by the antibody.

Amino Acid Sequence↗

[Corneal ulcer and Behçet disease. Apropos of a case].

We report a case of a peripheral corneal ulcer that occurred to a 33 years old female with a Behçet's disease. This patient had a previous history of viral keratoconjunctivitis with subepithelial nodules one year ago. The type, aspect and localization of the ulcer suggested an immunologic origin. The evolution was favourable after systemic and local steroid therapy. The other aetiologies of such ulcer are discussed by the authors.

Adult↗

Propagation of pseudorabies virus in the nervous system of the mouse after intranasal inoculation.

The propagation of pseudorabies virus (PrV) in the mouse nervous system was studied after intranasal inoculation of a PrV mutant expressing beta-galactosidase after insertion of the Escherichia coli Lac-Z gene into the gene encoding the nonstructural, nonessential glycoprotein gG. This allowed rapid detection of infected cells by a single step reaction with the substrate X-gal. The gG-beta-gal+ mutant behaved like the wild-type Kaplan strain of origin. The incubation period was very short and the animals did not survive more than 52 hr after inoculation. In the nasal cavity, the virus infected almost exclusively the respiratory epithelium. The virus propagated to the nervous system via three neuronal pathways: (i) the trigeminal route, with primary infection in the trigeminal ganglion followed by anterograde transneuronal transfer to the spinal trigeminal nucleus; (ii) the sympathetic route, with a first cycle of replication in the superior cervical ganglion and retrograde transneuronal transfer to sympathetic preganglionic neurons in the intermediolateral nucleus in the spinal cord; and (iii) the parasympathetic route, with primary infection in the pterygopalatine ganglion, followed by retrograde transneuronal transfer and replication in the superior salivatory nucleus. In contrast, the olfactory system was rarely found infected, probably because of the short survival of the animals.

Animals↗

Vaccination against rabies: construction and characterization of SAG2, a double avirulent derivative of SADBern.

A double avirulent mutant was isolated from the SADBern strain of rabies virus by two successive selection steps using neutralizing anti-glycoprotein monoclonal antibodies. Both mutations affect the triplet coding for amino acid 333 of the glycoprotein. The resulting virus, called SAG2, has a glutamate coded by GAA in position 333 instead of an arginine. This new codon differs by two nucleotides from all the arginine triplets. SAG2 is avirulent in adult mice by intracerebral and intramuscular routes and it protects mice against a challenge by the CVS strain. This double mutant is still avirulent after three successive passages in suckling mouse brain or after ten successive cycles of multiplication in cell culture. Because it is protective and genetically stable, SAG2 represents an improvement on SAG1 which is already used for oral vaccination of foxes in Switzerland and France. It could also be a candidate for oral vaccination of dogs against rabies.

Animals↗

Compared optical performances of multifocal and monofocal intraocular lenses (contrast sensitivity and dynamic visual acuity)

The functional results (contrast sensitivity and dynamic visual acuity) of 19 multifocal (3M design) and 14 all polymethylmethacrylate biconvex monofocal intraocular lenses (IOLs), 6 mm in optical diameter were compared. Best corrected visual acuity was > or = 8/10 (Monoyer chart) Parinaud 2 in all cases. Major differences of functional performance in favour of monofocal IOLs were found outside standard conditions of vision (low contrast and illumination levels). A significant difference in contrast sensitivity was found for each spatial frequency in favour of multifocal IOLs (0.0016 < p < 0.05). Mesopic vision was statistically higher in the monofocal IOL group (p = 0.0015). Moreover, dynamic visual acuity allowed accurate evaluation of the difference in performance between these two models of implant. In view of these results multifocal IOLs should be reserved for patients with normal psychosensitive adaptation; an ocular pathology that could alter contrast sensitivity or mesopic vision is a contraindication for multifocal IOLs.

Aged↗

[Combined cataract-glaucoma operations. Extracapsular extraction and trabeculectomy versus phacoemulsification and trabeculectomy].

This retrospective study was conducted to evaluate the results of Combined Surgery of Cataract and Glaucoma (triple procedure). The procedure of combined surgery were trabeculectomy and extracapsular extraction (14 eyes) versus trabeculectomy and phacoemulsification (15 eyes). The follow-up of both groups was at least 9 months and up to 16 months (mean: 12 months). The mean decrease of IOP was 12.4 mmHg and 8.9 mm Hg in the first and second group respectively. Instillation of Beta-blockers twelve months after surgery were more frequent in the first group (64.3%) than in the second (26.7%). Finally, the IOP values one year after surgery were equivalent in both groups (less than 19 mmHg in 93% of cases). The mean features to emphasize the delay of recuperation of the best corrected visual acuity: one month for phacotrabeculectomy, and three months for extracapsular with trabeculectomy. The frequency of complications was low in both groups. We observed more hyphemas but less secondary cataracts in the phacotrabeculectomy group. Phacotrabeculectomy could become a reference procedure for combined glaucoma and cataract surgery.

Aged↗