1. Fundam Clin Pharmacol. 2010 Jun 22. [Epub ahead of print]
Reduced cardiac remodelling and prevention of glutathione deficiency after
omega-3 supplementation in chronic heart failure.
Fang Y, Favre J, Vercauteren M, Laillet B, Remy-Jouet I, Skiba M, Lallemand F,
Dehaudt C, Monteil C, Thuillez C, Mulder P.
INSERM U644, Institut Fédératif de Recherches Multidisciplinaires sur les
Peptides n degrees 23, Rouen Institut for Biomedical Research and Inovation, UFR
de Médecine et de Pharmacie, 22 Boulevard Gambetta, 76183 Rouen, France.
Abstract n-3 polyunsaturated fatty acids (omega-3) supplementation is associated
with reduced cardiovascular mortality and post-infarction death. However, the
impact of omega-3 supplementation in congestive heart failure (CHF) is still
unknown. This study assesses the effects of omega-3 supplementation on left
ventricular (LV) function and remodelling. We assessed, in rats with CHF induced
by left coronary ligation, the effects of a 1-week and a 12-week supplementation
with omega-3 (450 mg/kg per day) on LV hemodynamics, function and structure.
Chronic omega-3 reduces total peripheral resistance due to an increase in cardiac
output without modification of arterial pressure. Only chronic omega-3 reduces LV
end-diastolic pressure and LV relaxation constant. Moreover, chronic omega-3
decreases LV systolic and diastolic diameters, LV weight and collagen density.
Acute and chronic omega-3 increase LV gamma-glutamyl-cysteine synthetase and
oppose glutathione deficiency resulting in a reduction of myocardial oxidized
glutathione. In experimental CHF, long-term omega-3 supplementation improves LV
hemodynamics and function and prevents LV remodelling and glutathione deficiency.
The latter might be one of the mechanisms involved, but whether other mechanism,
independent of myocardial redox 'status', such as reduced inflammation, are
implicated remains to be confirmed.
PMID: 20584202 [PubMed - as supplied by publisher]
2. Gynecol Obstet Fertil. 2010 Jun 23. [Epub ahead of print]
[Surgical treatment of tubo-ovarian abscess occurring in deep endometriosis.]
[Article in French]
Mokdad C, Rozsnayi F, Delaunay F, Gregorczyk V, Auber M, Puscasiu L, Marpeau L,
Roman H.
Clinique gynécologique et obstétricale, CHU Charles-Nicolle, 1, rue de Germont,
76031 Rouen, France.
Tubo-ovarian abscesses are likely to occur in women suffering from deep
endometriosis. The aim of surgical management of tubo-ovarian abscesses is the
laparoscopic drainage, while deep endometriosis resection should be delayed.
Laparoscopic procedure carried out in emergency does not attempt at the excision
of deep endometriotic lesions, and must avoid the choice of the laparoconversion,
in order to avoid further changes in the pelvic anatomy rendering more difficult
a curative surgery. We report six cases of patients presenting tubo-ovarian
abscesses arising on deep endometriosis, and we discuss the choice of the 2-step
surgical management. In four cases, deep endometriosis resection has been
performed by laparoscopic route few months after the drainage of abscess and
provided macroscopically complete excision of the disease. Copyright © 2010
Elsevier Masson SAS. All rights reserved.
PMID: 20579921 [PubMed - as supplied by publisher]
3. Gynecol Obstet Fertil. 2010 Jun 23. [Epub ahead of print]
[Predictive value of uterine artery velocity waveforms in monitoring of
pregnancies with high obstetrical risk antiphospholipid syndrome: The Rouen
experience.]
[Article in French]
Seror J, Verspyck E, Borg JY, Berkane N, Marpeau L.
Clinique gynécologique et obstétricale, CHU de Rouen, 1, rue de Germont, 76031
Rouen cedex, France; UPMC université Paris 06, 75005 Paris, France; Service de
gynécologie-obstétrique et médecine de la reproductive, hôpital Tenon, 4, rue de
la Chine, AP-HP, 75970 cedex 20 Paris, France.
OBJECTIVES: Anti-phospholipid syndrome (APLS) and obstetrical complications have
been associated for years. The purpose of this study was to define a high
obstetrical risk subpopulation of APLS and search predictive criteria of
complications likely to improve monitoring of pregnancy. PATIENTS AND METHODS: We
conducted a retrospective study at the CHU of Rouen between 1998 and January
2008. Pregnancies were included for patients with APLS according to the criteria
of Sydney without repeated miscarriages item. RESULTS: The study involved 20
pregnancies from eight patients. Fourteen pregnancies gave birth to living
children or 70 %, 28.6 % were complicated with pre-eclampsia, 50 % of haemolysis
elevated liver enzymes low platelets (HELLP) syndrome associated with a 28.6 %
stunting and 42 % of premature birth. Patients received treatment involving
aspirin and heparin. The obstetrical prognosis was significantly poorer in the
subgroup with APLS notch bilateral persistent middle of the term of birth of 35.5
versus 28 weeks of gestation, and median birth weight of 950g versus 2780g
(p<0.05). DISCUSSION AND CONCLUSION: Patients were selected according to the more
specific criteria of APLS (thrombosis and fetal loss) and a history of severe
obstetrical complications. In some series, these complications play a major role;
in others, they are unsignificant. Rate, in this study, is high (47 %) and the
presence of bilateral notch seems to be an excellent predictive marker of
vascular complications in this population. Copyright © 2010 Elsevier Masson SAS.
All rights reserved.
PMID: 20579918 [PubMed - as supplied by publisher]
4. Rev Med Interne. 2010 Jun 22. [Epub ahead of print]
[TRAPS: Clinical significance of genotype. A report of two cases.]
[Article in French]
Lahaxe L, Josse S, Grateau G, Levesque H, Marie I.
Département de médecine interne, CHU de Rouen, 1 rue de Germont, 76031 Rouen
cedex, France.
INTRODUCTION: Tumor necrosis factor receptor associated periodic fever syndrome
(TRAPS) is defined as recurrent attacks of generalized inflammation for which no
infectious or auto-immune cause can be identified; it is caused by dominantly
inherited mutations in the gene encoding the first TNF receptor. We report two
additional cases of patients with TRAPS, suggesting that mutation pattern of
TNFRSF 1A gene may influence the TRAPS phenotype. CASE REPORTS: The first
patient, with a C30S mutation, exhibited severe digestive clinical
manifestations; because the patient required high-dose corticosteroids regimen to
improve TRAPS manifestations, he was further given successfully etanercept. The
second patient, with a R92Q mutation of TNFRSF 1A gene, presented with moderate
symptoms; TRAPS outcome was favourable after corticosteroid therapy initiation.
CONCLUSION: Therefore, R92Q may be associated with a mild disease phenotype. On
the other hand, C30S mutation appears to be associated with a severe phenotype,
leading to an increased risk of amyloidosis. These findings suggest that these
latter patients may require a closer follow-up. Copyright © 2010 Société
nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All
rights reserved.
PMID: 20576331 [PubMed - as supplied by publisher]
5. Mov Disord. 2010 Jun 21. [Epub ahead of print]
Psychogenic paralysis and recovery after motor cortex transcranial magnetic
stimulation.
Chastan N, Parain D.
Department of Neurophysiology, Rouen University Hospital, Rouen, France.
Psychogenic paralysis presents a real treatment challenge. Despite psychotherapy,
physiotherapy, antidepressants, acupuncture, or hypnosis, the outcome is not
always satisfactory with persistent symptoms after long-term follow-up. We
conducted a retrospective study to assess clinical features and to propose an
alternative treatment based on repetitive transcranial magnetic stimulation
(rTMS). Seventy patients (44 F/26 M, mean age: 24.7 +/- 16.6 years) experienced
paraparesis (57%), monoparesis (37%), tetraparesis (3%), or hemiparesis (3%). A
precipitating event was observed in 42 patients, primarily as a psychosocial
event or a physical injury. An average of 30 stimuli over the motor cortex
contralateral to the corresponding paralysis was delivered at low frequency with
a circular coil. The rTMS was effective in 89% of cases, with a significantly
better outcome for acute rather than chronic symptoms. In conclusion, motor
cortex rTMS seem to be very effective in patients with psychogenic paralysis and
could be considered a useful therapeutic option. (c) 2010 Movement Disorder
Society.
PMID: 20568093 [PubMed - as supplied by publisher]
6. Free Radic Biol Med. 2010 Jun 4. [Epub ahead of print]
Mitochondrial impairment contributes to cocaine-induced cardiac dysfunction:
Prevention by the targeted antioxidant MitoQ.
Vergeade A, Mulder P, Vendeville-Dehaudt C, Estour F, Fortin D, Ventura-Clapier
R, Thuillez C, Monteil C.
INSERM U644, University of Rouen, Rouen F-76183, France.
The goal of this study was to assess mitochondrial function and ROS production in
an experimental model of cocaine-induced cardiac dysfunction. We hypothesized
that cocaine abuse may lead to altered mitochondrial function that in turn may
cause left ventricular dysfunction. Seven days of cocaine administration to rats
led to an increased oxygen consumption detected in cardiac fibers, specifically
through complex I and complex III. ROS levels were increased, specifically in
interfibrillar mitochondria. In parallel there was a decrease in ATP synthesis,
whereas no difference was observed in subsarcolemmal mitochondria. This
uncoupling effect on oxidative phosphorylation was not detectable after
short-term exposure to cocaine, suggesting that these mitochondrial abnormalities
were a late rather than a primary event in the pathological response to cocaine.
MitoQ, a mitochondrial-targeted antioxidant, was shown to completely prevent
these mitochondrial abnormalities as well as cardiac dysfunction characterized
here by a diastolic dysfunction studied with a conductance catheter to obtain
pressure-volume data. Taken together, these results extend previous studies and
demonstrate that cocaine-induced cardiac dysfunction may be due to a
mitochondrial defect. Copyright © 2010. Published by Elsevier Inc.
PMID: 20566328 [PubMed - as supplied by publisher]
7. Cancer Gene Ther. 2010 Jun 18. [Epub ahead of print]
The soluble fragment of VE-cadherin inhibits angiogenesis by reducing endothelial
cell proliferation and tube capillary formation.
Li H, Shi X, Liu J, Hu C, Zhang X, Liu H, Jin J, Opolon P, Vannier JP,
Perricaudet M, Janin A, Soria C, Lu H.
[1] MERCI EA 3829, Faculté de Médecine et de Pharmacie, Université de Rouen,
Rouen, France [2] CNRS UMR 8121, Institut Gustave Roussy, Villejuif, France.
Vascular endothelial-specific cadherin (VE-cadherin) is an endothelial
cell-specific adhesion molecule, localized at cell-cell contact sites. It is
involved in physiological and pathological angiogenesis. In this study, we showed
that in vitro a soluble N-terminal fragment of VE-cadherin (EC1-3) corresponding
to cadherin 1-3 ectodomains inhibited vascular endothelial growth
factor-stimulated endothelial cell proliferation and capillary tube structure
formation in the matrigel model. In vivo, EC1-3 was tested in a murine colon
cancer model. EC1-3-expressing colon cancer C51 cells were subcutaneously grafted
into nude mice, and tumor growth and angiogenesis were evaluated. At day 33, the
mean volume of the tumors developed was reduced (510+/-104 versus 990+/-120 mm(3)
for control). Similarly, injection of EC1-3 virus-producing cells into
established C51 tumors resulted in an inhibition by 33% of tumor growth.
Immunohistological staining of vessels on tumor sections showed a significantly
reduced intratumoral angiogenesis. Furthermore, EC1-3 did not induce vessel
injury in the lung, liver, spleen, heart and brain in the mice. These results
suggest that the soluble N-terminal fragment of VE-cadherin EC1-3 could exert an
antitumoral effect by targeting tumor angiogenesis, which included blocking
endothelial cell proliferation and capillary tube formation with no obvious
toxicity on normal organs.Cancer Gene Therapy advance online publication, 18 June
2010; doi:10.1038/cgt.2010.26.
PMID: 20559333 [PubMed - as supplied by publisher]
8. J Nucl Med. 2010 Jun 16. [Epub ahead of print]
Leukocyte SPECT/CT for Detecting Infection of Left-Ventricular-Assist Devices:
Preliminary Results.
Litzler PY, Manrique A, Etienne M, Salles A, Edet-Sanson A, Vera P, Bessou JP,
Hitzel A.
Department of Thoracic and Cardiovascular Surgery, Rouen University Hospital,
Rouen, France; INSERM U644, University of Rouen, Rouen, France; Groupe de
Recherche sur les Antimicrobiens et les Micro-organismes (EA2656), University of
Rouen, Rouen, France.
We report our experience with using integrated molecular and anatomic hybrid
imaging to assess infection in patients who have a left-ventricular-assist device
(LVAD). METHODS: Thirteen (99m)Tc-exametazime-leukocyte planar and SPECT/CT scans
were obtained for 8 consecutive patients who had an implanted LVAD. SPECT/CT was
used to assess suspected device-related infections (n = 8) and to evaluate the
efficiency of current antibiotic therapy (n = 5). RESULTS: Device-related
infection was seen on 8 of the 13 scans. SPECT/CT was positive for infection in
all 8 patients, whereas planar scans were positive in 6 of 8. SPECT/CT provided
relevant information on the extent of infection and its exact location in all
patients. Additional distant infectious foci were demonstrated in 3 of 13
patients. CONCLUSION: SPECT/CT led to an accurate diagnosis of LVAD-related
infection, revealing both anatomic location and extent. This noninvasive approach
could lead to improved therapeutic strategies.
PMID: 20554736 [PubMed - as supplied by publisher]
9. Glia. 2010 Jun 14. [Epub ahead of print]
Comparative gene expression profiling of olfactory ensheathing cells from
olfactory bulb and olfactory mucosa.
Guérout N, Derambure C, Drouot L, Bon-Mardion N, Duclos C, Boyer O, Marie JP.
Experimental Surgery Laboratory, Groupe de Recherche sur le Handicap Ventilatoire
(GRHV), UPRES EA 3830, European Institute for Peptide Research (IFRMP 23),
Institute for Medical Research, Faculty of Medicine and Pharmacy, University of
Rouen, 22 boulevard Gambetta, 76183 Rouen, France.
Olfactory ensheathing cells (OEC) have the ability to promote regeneration in the
nervous system. Hence, they hold promise for cell therapy. Most of the
experimental studies have investigated the role of OECs taken from olfactory bulb
(OB). However, for a clinical human application, olfactory mucosa (OM) seems to
be the only acceptable source for OECs. Many studies have compared the distinct
ability of OECs from OB and OM to improve functional nerve regeneration after
lesion of the nervous system. Nevertheless, the two populations of OECs may
differ in several points, which might affect all fate after transplantation in
vivo. We report here the first study which compares gene expression profiling
between these two populations of OECs. It appears that OB-OECs and OM-OECs
display distinct gene expression pattern, which suggest that they may be
implicated in different physiological processes. Notably, OM-OECs overexpress
genes characteristic of wound healing and regulation of extra cellular matrix. In
contrast, OB-OECs gene profile suggests a prominent role in nervous system
development. Hence, OB-OECs and OM-OECs fundamentally differ in their gene
expression pattern, which may represent a crucial point for future clinical
application. (c) 2010 Wiley-Liss, Inc.
PMID: 20549746 [PubMed - as supplied by publisher]
10. Antimicrob Agents Chemother. 2010 Jun 14. [Epub ahead of print]
Baseline genotypic and phenotypic susceptibility of HIV-1 group O to enfuvirtide.
Depatureaux A, Charpentier C, Collin G, Leoz M, Descamps D, Vessière A, Damond F,
Rousset D, Brun-Vézinet F, Plantier JC.
Laboratoire associé au Centre National de Référence du VIH, EA2656, CHU Charles
Nicolle, Rouen, France; Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital
Bichat-Claude Bernard, Laboratoire de Virologie, Paris, France; Centre Pasteur du
Cameroun, Yaoundé, Cameroon.
We assessed the natural genotypic and phenotypic susceptibility to enfuvirtide of
171 HIV-O samples and 29 strains, respectively. The N42D resistance-associated
mutation in the gp41 region was detected in 98% of cases. The phenotypic assay
showed a wide range of baseline susceptibility, with IC50 values from 4 to 5,000
nM, similar to the range described for HIV-1 group M. Thus, despite the natural
genotypic resistance conferred by the N42D signature mutation, HIV-O variants
appear to be phenotypically susceptible. Enfuvirtide could therefore potentially
be used in antiretroviral treatments for HIV-O-infected patients.
PMID: 20547806 [PubMed - as supplied by publisher]
11. Arch Pediatr. 2010 Jun 7. [Epub ahead of print]
[Administration of a single winter oral dose of 200,000 IU of vitamin D(3) in
adolescents in Normandy: Evaluation of the safety and vitamin D status obtained.]
[Article in French]
Mallet E, Philippe F, Castanet M, Basuyau JP.
Département de pédiatrie médicale, CIC Inserm 204, CHU Charles-Nicolle, 1, rue de
Germont, 76031 Rouen cedex, France.
Adolescence, a period of growth and acquisition of bone mass, requires adequate
calcium and vitamin D intake. This study was designed to assess the impact of a
single loading dose of 200,000 IU of vitamin D(3) on the winter vitamin D status
of healthy adolescents. Vitamin D status was assessed by 25-OH-D levels before, 3
weeks, and 3 months after this single dose, and safety was assessed by serum
calcium and PTH and urinary calcium excretion in random samples from 27, 23, and
17 healthy adolescents derived from the same institution. The 25-OH-D peak value
2 weeks after the vitamin D supplement of 71-129 nmol/l (mean, 96 nmol/l), and a
residual level at 3 months of 29-83 nmol/l (mean, 57 nmol/l) serum calcium and
urinary calcium excretion expressed by the calcium/creatinine ratio were normal
and stable at 2 weeks and 3 months, remaining less than 0.5 for the
calcium/creatinine ratio. This simple measure, ensuring good compliance during
adolescence, ensures optimal winter vitamin D status with no signs of overload.
Copyright © 2010 Elsevier Masson SAS. All rights reserved.
PMID: 20542672 [PubMed - as supplied by publisher]
12. Rev Med Interne. 2010 Jun 8. [Epub ahead of print]
[Woody hands.]
[Article in French]
Roca F, Cailleux N, Benhamou Y, Scotte M, Lévesque H, Marie I.
Département de médecine interne, CHU de Rouen, 1, rue de Germont, 76031 Rouen
cedex, France.
PMID: 20538388 [PubMed - as supplied by publisher]
13. Transpl Int. 2010 Jun 7. [Epub ahead of print]
Comparative effects of sirolimus and cyclosporin on conduit arteries endothelial
function in kidney recipients.
Joannides R, Etienne I, Iacob M, de Ligny BH, Barbier S, Bellien J, Lebranchu Y,
Thuillez C, Godin M.
Department of Pharmacology, Rouen University Hospital & INSERM U644, Institute
for Biomedical Research, University of Rouen, Rouen, France.
Summary This study attempted to establish whether a calcineurin inhibitor
(CNI)-free immunosuppressant regimen based on sirolimus (SRL) is associated with
a preservation of conduit arteries endothelial function in kidney recipients or
not. Twenty-nine kidney recipients were randomized to receive since
transplantation SRL (n = 15) or cyclosporin A (CsA, n = 14) associated with
mycophenolate mofetil (MMF) and steroids (6 months) in a parallel prospective
study. Systolic, diastolic blood pressures, glomerular filtration rate (GFR) and
radial artery flow-mediated dilatation (FMD) induced by postischaemic hyperaemia
were assessed in a blind manner at one (M1) and 7 months (M7) after
transplantation. Endothelium-independent dilatation was assessed by glyceryl
trinitrate spray. There was no difference between the groups for all vascular
parameters at M1. At M7, systolic blood pressure was lower (SRL: 119 +/- 3 vs.
CsA: 138 +/- 4 mmHg, P < 0.05) and FMD was higher in SRL compared with CsA (SRL:
13.1 +/- 0.9 vs. CsA: 9.9 +/- 0.9%, P < 0.05) without any difference for
hyperaemia, endothelium-independent dilatation and GFR (SRL: 66.7 +/- 1.05 vs.
CsA: 67.5 +/- 1.22 ml/min). Our results demonstrate that a CNI-free regimen based
on SRL and MMF prevents conduit artery endothelial dysfunction compared with CsA
and MMF in kidney recipients suggesting a beneficial arterial wall effect that
may also contribute to the decrease in systolic blood pressure.
PMID: 20536790 [PubMed - as supplied by publisher]
14. Rev Infirm. 2010 Jun;(161):21-2.
[In Process Citation]
[Article in French]
Carvalho P, Touflet M.
CHU de Rouen. priscille.carvalho@chu-rouen.fr
PMID: 20536086 [PubMed - in process]
15. Rheumatology (Oxford). 2010 Jun 4. [Epub ahead of print]
Psychopathological and personality features in primary Sjogren's
syndrome--associations with autoantibodies to neuropeptides.
Karaiskos D, Mavragani CP, Sinno MH, Déchelotte P, Zintzaras E, Skopouli FN,
Fetissov SO, Moutsopoulos HM.
Department of Pathophysiology, Department of Experimental Physiology, School of
Medicine, University of Athens, Athens, Greece, Digestive System and Nutrition
Laboratory, Institute of Biomedical Research, Rouen University and Hospital,
Rouen, France, Department of Biomathematics, University of Thessaly School of
Medicine, Larissa and Department of Human Nutrition and Dietetics, Harokopio
University of Athens, Athens, Greece.
Objectives. To determine the spectrum of personality and psychopathology features
of patients with primary SS (pSS) and explore whether they are linked to disease
characteristics as well as the presence of autoantibodies (autoAbs) against
neuropeptides. Methods. Personality and psychopathological variables were
determined in 103 pSS patients and 110 healthy controls (HCs). AutoAbs against
hypothalamic and pituitary neuropeptides were measured by ELISA in 25 pSS
patients and 25 HCs. Data analysis was performed by univariate and multivariate
logistic regression models and by comparison with regression models. Results. A
higher number of pSS patients reported distinct personality traits (neuroticism,
psychoticism and obsessiveness) and psychological distress compared with HCs.
After adjustment for personality characteristics and demographics, only
hypochondriasis was the main psychopathology feature associated with pSS,
suggesting that psychopathological manifestations in the setting of pSS are
primarily dependent on premorbid personality characteristics. Although no
differences were detected between serum levels of neuropeptide autoAbs in pSS
cases and controls, levels of autoAbs against alpha-melanocyte-stimulating
hormone (alpha-MSH) correlated with anxiety scores in both groups examined but
with higher intercept in pSS subjects. Significant correlations between anxiety
score and autoAbs directed against oxytocin and vasopressin were also detected in
the pSS patients. Conclusions. pSS patients exhibit a distinct pattern of
personality traits and high levels of psychological distress compared with HCs,
which seems to be determined by premorbid personality characteristics.
Correlations between anxiety and alpha-MSH autoAbs suggest their potential
involvement in anxiety development in both pSS and HCs.
PMID: 20525741 [PubMed - as supplied by publisher]
16. Hum Mutat. 2010 Jun 3. [Epub ahead of print]
Type I hyperprolinemia: genotype/phenotype correlations.
Guilmatre A, Legallic S, Steel G, Willis A, Di Rosa G, Goldenberg A,
Drouin-Garraud V, Guet A, Mignot C, Des Portes V, Valayannopoulos V, Van
Maldergem L, Hoffman JD, Izzi C, Espil-Taris C, Orcesi S, Bonafé L, Le Galloudec
E, Maurey H, Ioos C, Afenjar A, Blanchet P, Echenne B, Roubertie A, Frebourg T,
Valle D, Campion D.
Inserm U614, IHU, Rouen, France.
Type I hyperprolinemia (HPI) is an autosomal recessive disorder associated with
cognitive and psychiatric troubles, caused by alterations of the Proline
Dehydrogenase gene (PRODH) at 22q11. HPI results from PRODHdeletion and/or
missense mutations reducing proline oxidase (POX) activity. The goals of this
study were first to measure in controls the frequency of PRODHvariations
described in HPI patients, second to assess the functional effect of PRODH
mutations on POX activity and finally to establish genotype/enzymatic activity
correlations in a new series of HPI patients. 8/14 variants occurred at
polymorphic frequency in 114 controls. POX activity was determined for 6 novel
mutations and 2 haplotypes. The c.1331G>A, p.G444D allele has a drastic effect
whereas the c.23C>T, p.P8L allele and the c.[56C>A; 172G>A], p.[Q19P; A58T]
haplotype result in a moderate decrease in activity. Among the 19 HPI patients,
10 had a predicted residual activity < 50%. 8 out of 9 subjects with a predicted
residual activity >/=50% bore at least one c.824C>A, p.T275N allele, which has no
detrimental effect on activity but whose frequency in controls is only 3%. Our
results suggest that PRODH mutations lead to a decreased POX activity or affect
other biological parameters causing hyperprolinemia. (c) 2010 Wiley-Liss, Inc.
PMID: 20524212 [PubMed - as supplied by publisher]
17. J Med Genet. 2010 Jun;47(6):398-403.
The BRCA1 c.5434C->G (p.Pro1812Ala) variant induces a deleterious exon 23
skipping by affecting exonic splicing regulatory elements.
Gaildrat P, Krieger S, Théry JC, Killian A, Rousselin A, Berthet P, Frébourg T,
Hardouin A, Martins A, Tosi M.
Inserm U614, Faculty of Medicine, 22 Boulevard Gambetta, 76183 Rouen, France.
BACKGROUND A large fraction of the sequence variants of unknown significance or
unclassified variants (UVs) could be pathogenic by affecting mRNA splicing. The
breast and ovarian cancer susceptibility gene BRCA1 exhibits a large spectrum of
sequence variation but only two variants, both located in exon 18, have been
shown experimentally to affect splicing regulatory elements. The present study
investigated the impact on splicing of the variant BRCA1 c.5434C-->G
(p.Pro1812Ala), identified in an ovarian cancer patient. This variant has
previously been studied at the protein level with inconclusive results concerning
its pathogenic role. METHODS Analysis of RNA from patient peripheral blood was
performed by RT-PCR. The effect of the variant was tested by using splicing
reporter hybrid minigene assays. RESULTS Using patient RNA analyses and hybrid
minigene assays, we showed that this variant induces a major splicing defect,
with skipping of exon 23, resulting in frameshift and predicted protein
termination within the second BRCT domain. Moreover, we showed that the segment
c.5420-5449 of BRCA1, in the centre of exon 23, exhibits splicing enhancer
properties. This enhancement is abolished by the c.5434C-->G mutation, indicating
that the nucleotide change, in this highly conserved region, affects a splicing
regulatory element. Bioinformatics analyses predict that the mutation c.5434C-->G
creates an hnRNPA1 dependent splicing silencer. CONCLUSION These data, together
with segregation data, argue for the classification of BRCA1 c.5434C-->G as a
pathogenic splicing mutation. These results also suggest that UVs in highly
conserved nucleotide sequences of short exons may be good candidates for
detecting functionally relevant splicing regulatory elements.
PMID: 20522429 [PubMed - in process]
18. Interact Cardiovasc Thorac Surg. 2010 Jun 1. [Epub ahead of print]
Acute aortic syndrome: a 'last glance' before incision.
Lebreton G, Litzler PY, Bessou JP, Doguet F.
Division of cardiac surgery, Universitary hospital of Rouen, France.
Acute aortic syndrome (AAS) (aortic dissection, intramural aortic haematoma, or
penetrating atherosclerotic ulcer) is a surgical emergency. Computed tomography
(CT) is the reference technique for the diagnosis of this critical situation.
However, a few reports of false-positive images leading to unnecessary
interventions have been published. It is important to recognize and understand
the pitfalls in the CT diagnosis of AAS. We describe the case of a 76-year-old
man with clinical signs of AAS and a CT-scan compatible with a diagnosis of
aortic intra-mural haematoma, leading to emergency surgery. The peroperative
findings revealed a normal aortic wall with the presence of an unusual
pericardial recess at the right side of the aorta. Keywords: Acute aortic
syndrome; Computed tomography; Transthoracic echocardiography; Transoesophageal
echocardiography.
PMID: 20515919 [PubMed - as supplied by publisher]
19. Endocr Relat Cancer. 2010 Jun 25;17(3):637-51. Print 2010.
Expression of trophic amidated peptides and their receptors in benign and
malignant pheochromocytomas: high expression of adrenomedullin RDC1 receptor and
implication in tumoral cell survival.
Thouënnon E, Pierre A, Tanguy Y, Guillemot J, Manecka DL, Guérin M, Ouafik L,
Muresan M, Klein M, Bertherat J, Lefebvre H, Plouin PF, Yon L, Anouar Y.
INSERM, U982, Laboratory of Neuronal and Neuroendocrine Differentiation and
Communication (DC2N), IFRMP23, University of Rouen, 76821 Mont-Saint-Aignan,
France.
Pheochromocytomas are catecholamine-producing tumors which are generally benign,
but which can also present as or develop into malignancy. Molecular pathways of
malignant transformation remain poorly understood. Pheochromocytomas express
various trophic peptides which may influence tumoral cell behavior. Here, we
investigated the expression of trophic amidated peptides, including pituitary
adenylate cyclase-activating polypeptide (PACAP), neuropeptide Y (NPY), and
adrenomedullin (AM), and their receptors in benign and malignant
pheochromocytomas in order to assess their potential role in chromaffin cell
tumorigenesis and malignant transformation. PACAP, NPY, and AM are expressed in
the majority of pheochromocytomas studied; NPY exhibiting the highest mRNA levels
relative to reference genes. Although median gene expression or peptide levels
were systematically lower in malignant compared to benign tumors, no
statistically significant difference was found. Among all the receptors of these
peptides that were analyzed, only the AM receptor RDC1 displayed a differential
expression between benign and malignant pheochromocytomas. This receptor
exhibited a fourfold higher expression in malignant than in benign tumors. AM and
stromal cell-derived factor 1, which has also been described as a ligand for
RDC1, increased the number of human pheochromocytoma cells in primary culture and
exerted anti-apoptotic activity on rat pheochromocytoma PC12 cells. In addition,
RDC1 gene silencing decreased the number of viable PC12 cells. This study shows
the expression of several trophic peptides and their receptors in benign and
malignant pheochromocytomas, and suggests that AM and its RDC1 receptor could be
involved in chromaffin cell tumorigenesis through pro-survival effects.
Therefore, AM and RDC1 may represent valuable targets for the treatment of
malignant pheochromocytomas.
PMID: 20483910 [PubMed - in process]
20. World J Biol Psychiatry. 2010 Jun;11(4):604-55.
The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for
the biological treatment of paraphilias.
Thibaut F, De La Barra F, Gordon H, Cosyns P, Bradford JM; WFSBP Task Force on
Sexual Disorders.
Collaborators: Thibaut F, Cosyns P, Bradford JM, de la Barra F, Gordon H, Rosler
A.
Faculty of Medicine, Rouen University Hospital Ch. Nicolle, University of Rouen,
Rouen, France. florence.thibaut@chu-rouen.fr
OBJECTIVES: The primary aim of these guidelines was to evaluate the role of
pharmacological agents in the treatment and management of paraphilia, with a
focus on the treatment of adults males. Because such treatments are not delivered
in isolation, the role of specific psychosocial and psychotherapeutic
interventions was also briefly covered. These guidelines are intended for use in
clinical practice by clinicians who diagnose and treat patients with paraphilia.
The aim of these guidelines is to improve the quality of care and to aid
physicians in clinical decisions. METHODS: The aim of these guidelines was to
bring together different views on the appropriate treatment of paraphilias from
experts representing different continents. To achieve this aim, an extensive
literature search was conducted using the English language literature indexed on
MEDLINE/PubMed (1990-2009 for SSRIs) (1969-2009 for antiandrogen treatments),
supplemented by other sources, including published reviews. RESULTS: Each
treatment recommendation was evaluated and discussed with respect to the strength
of evidence for its efficacy, safety, tolerability and feasibility. CONCLUSIONS:
An algorithm was proposed with six levels of treatment for different categories
of paraphilias.
PMID: 20459370 [PubMed - in process]
21. Chir Main. 2010 Jun;29(3):188-94. Epub 2010 Apr 22.
[Arthroscopic partial trapezectomy. A radio-anatomical study about 14 cases]
[Article in French]
Beldame J, Desmoineaux P, Le Moulec YP, Lintz F, Duparc F.
Service d'orthopédie traumatologique-SOS main, CHU de Rouen, 76031 Rouen cedex,
France.
OBJECTIVES: The aim of the study was to assess the accessibility of the trapezium
surface to arthroscopic resection related to the degenerative stage, to define
the surgical approach and to determine the efficacy of the X-rays for evaluating
the amount of resected bone. METHODS: Fourteen trapezectomies were performed on
seven cadaveric specimens using an arthroscopic procedure. Pre- and
post-procedure X-rays were used to assess the initial trapeziometacarpal
osteoarthritis and the resection performed. Each subject was randomized for using
two posterior portals or two posterior portals and one anterior portal. At the
end of the procedure, a dissection was performed for evaluating the quality of
resection and the anatomical relationship of each surgical approach. RESULTS: The
stages of preprocedure osteoarthritis were comparable between the two sides of
the same cadaveric specimen. On post-procedure X-rays, the resection appeared
complete in only six out of 14 wrists. During dissection, no injury to
neurovascular structures was observed, and the resection was visible
macroscopically in 11/14 wrists. Three resections were incomplete, i.e., less
than 20 % of total trapezial surface: two of them were seen in the most
osteoarthritic cases of the study. CONCLUSIONS: The arthroscopic approach
presents an opportunity to access the entire trapezial surface, even if a high
stage of osteoarthritis appears to be a risk for incomplete resection. The
addition of a systematic anterior approach to the traditional dorsal approach
does not increase the accessibility. Although radiography is not the most
appropriate tool to assess the resected surface, it does help to locate the
defects of resection and can guide the surgical procedure in situations where
there is a risk of incomplete resection. Copyright 2010. Published by Elsevier
SAS.
PMID: 20452808 [PubMed - in process]
22. Hum Reprod. 2010 Jun;25(6):1428-32. Epub 2010 Apr 8.
Direct proportional relationship between endometrioma size and ovarian parenchyma
inadvertently removed during cystectomy, and its implication on the management of
enlarged endometriomas.
Roman H, Tarta O, Pura I, Opris I, Bourdel N, Marpeau L, Sabourin JC.
Department of Gynaecology and Obstetrics, and Groupe de recherche EA 4308
Spermatogenesis and Male Gamete Quality, Rouen University Hospital, 76031 Rouen,
France. horace.roman@gmail.com
BACKGROUND: The aim of this study was to estimate whether or not the size of an
endometrioma is related to the thickness of the ovarian parenchyma inadvertently
excised along with the cyst wall. METHODS: We performed a retrospective study
including 35 women who had undergone endometrioma cystectomy, using an ovarian
tissue sparing procedure. In total 38 specimens were studied by three
pathologists as three women presented bilateral localizations, and all cyst
diameters measured at least 30 mm. For each endometrioma, serial sections were
performed, and on each section four different sites were randomly chosen to
measure the thickness of glandular epithelium and stroma, of subjacent fibrosis,
depending on the cyst, and of the ovarian parenchyma removed with the cyst. The
diameter of the ovary was measured preoperatively either by MRI or ultrasound,
and the area of the internal wall was then calculated. The relationships between
the mean thickness of ovarian parenchyma removed and the variables were estimated
and a multiple regression model identified independent predictors for ovarian
parenchyma thickness. RESULTS: Adjacent ovarian tissue was found in 37 cases
(97%). The mean thickness of ovarian tissue removed was 1173 +/- 711 microm and
that of the cyst wall was 851 +/- 499 microm. The thickness of the ovarian
parenchyma removed presented a direct proportional relationship with cyst
diameter (P = 0.015), and consequently with cyst wall area (P = 0.032). This
relationship with cyst diameter was independent after adjustment on other
variables (P = 0.032). CONCLUSION: Endometrioma cystectomy even though performed
with an accurate surgical technique leads to significant ovarian tissue removal,
the thickness of which increases proportionally with cyst diameter.
PMID: 20378613 [PubMed - in process]
23. Acta Neuropathol. 2010 Jun;119(6):779-89. Epub 2010 Apr 8.
Human lissencephaly with cerebellar hypoplasia due to mutations in TUBA1A:
expansion of the foetal neuropathological phenotype.
Lecourtois M, Poirier K, Friocourt G, Jaglin X, Goldenberg A, Saugier-Veber P,
Chelly J, Laquerrière A.
Faculty of Medicine, INSERM, U614, IFRMP23, Rouen Institute for Medical Research
and Innovation, University of Rouen, Rouen, France.
Neuronal migration disorders account for a substantial number of cortical
malformations, the most severe forms being represented by lissencephalies.
Classical lissencephaly has been shown to result from mutations in LIS1
(PAFAH1B1; MIM#601545), DCX (Doublecortin; MIM#300121), ARX (Aristaless-related
homeobox gene; MIM#300382), RELN (Reelin; MIM#600514) and VLDLR (Very low density
lipoprotein receptor; MIM#224050). More recently, de novo missense mutations in
the alpha-tubulin 1a gene (TUBA1A) located on chromosome 12q13.12, have also been
associated with more or less severe defects of cortical development, resulting in
complete agyria in the most severe cases of lissencephaly. We report here the
cerebral lesions in a 36 weeks' gestation female foetus with a novel de novo
missense mutation in the TUBA1A gene, presenting the most severe antenatal
phenotype reported so far. Using routine immunohistochemistry and confocal
microscopy, we show evidence for defects in axonal transport in addition to
defects in neuronal migration and differentiation, giving new insights to the
pathophysiology of this form of lissencephaly.
PMID: 20376468 [PubMed - in process]
24. J Neurosurg. 2010 Jun;112(6):1200-7.
Interdisciplinary treatment of ruptured cerebral aneurysms in elderly patients.
Proust F, Gérardin E, Derrey S, Lesvèque S, Ramos S, Langlois O, Tollard E,
Bénichou J, Chassagne P, Clavier E, Fréger P.
Department of Neurosurgery, Rouen University Hospital, Rouen, France.
Francois.Proust@chu-rouen.fr
Comment in:
J Neurosurg. 2010 Jun;112(6):1197-8; discussion 1198-9.
OBJECT: The aim of the study was to assess postprocedural neurological
deterioration and outcome in patients older than 70 years of age in whom
treatment was managed in an interdisciplinary context. METHODS: This prospective
longitudinal study included all patients 70 years of age or older treated for
ruptured cerebral aneurysm over 10 years (June 1997-June 2007). The population
was composed of 64 patients. The neurovascular interdisciplinary team jointly
discussed the early obliteration procedure for each aneurysm. Neurological
deterioration during the postprocedural 2 months and outcome at 6 months were
assessed during consultation according to the modified Rankin Scale (mRS) as
follows: favorable (mRS score < or = 2) and unfavorable (mRS score > 2). RESULTS:
Aneurysm sac obliteration was performed by microvascular clipping in 34 patients
(53.1%) and by endovascular coiling in 30 (46.9%). Postprocedural neurological
deterioration occurred in 30 patients (46.9%), related to ischemia in 19 (29.7%),
rebleeding in 1 (1.6%), and hydrocephalus in 10 (15.6%). At 6 months, the outcome
was favorable in 39 patients (60.9%). By multivariate regression logistic
analysis, the independent factors associated with unfavorable outcome were age
exceeding 75 years (p = 0.005), poor initial grade (p < 0.0001), and the
occurrence of ischemia (p < 0.0001). CONCLUSIONS: The baseline characteristics of
SAH in the elderly were only slightly different from those in younger patients.
In the elderly, the interdisciplinary approach may be considered useful to
decrease the ischemic consequences.
PMID: 19961311 [PubMed - indexed for MEDLINE]
25. Presse Med. 2010 Jun;39(6):640-4.
[Mallory-Weiss syndrome: diagnosis and treatment]
[Article in French]
Lecleire S, Antonietti M, Ducrotté P.
Unité d'endoscopie digestive, Département d'hépato-gastroentérologie et
nutrition, Rouen Cedex, France. stephane.lecleire@chu-rouen.fr
Mallory-Weiss syndrome is relatively common and is involved in 3 to 10% of cases
of upper gastrointestinal bleeding. Most of the time, the hemorrhage is mild and
stops spontaneously. Clinical suspicion requires confirmation by an upper
gastrointestinal endoscopy, which must be performed rapidly after the first
hematemesis. Mallory-Weiss syndrome is diagnosed when it shows a longitudinal
mucosal tear at the esophagogastric junction. Patients with active bleeding or
signs of recent bleeding at endoscopy need immediate endoscopic treatment for
hemostasis. Band ligation seems to be the most efficient procedure for primary
hemostasis and for preventing recurrent bleeding. The use of proton pump
inhibitors and antiemetics seems logical in all cases, although nothing in the
literature demonstrates their efficacy. Copyright 2009 Elsevier Masson SAS. All
rights reserved.
PMID: 19931377 [PubMed - indexed for MEDLINE]
26. Presse Med. 2010 Jun;39(6):736-7. Epub 2009 Nov 6.
[Oral ulcerations...]
[Article in French]
Leblanc C, Lahaxe L, Girszyn N, Levesque H, Marie I.
Département de médecine interne, CHU Rouen, F-76031 Rouen Cedex, France.
PMID: 19896794 [PubMed - indexed for MEDLINE]
27. J Neurosurg. 2010 Jun;112(6):1263-6.
Alleviation of off-period dystonia in Parkinson disease by a microlesion
following subthalamic implantation.
Derrey S, Lefaucheur R, Chastan N, Gérardin E, Hannequin D, Desbordes M, Maltête
D.
Department of Neurosurgery, Rouen University Hospital and University of Rouen,
France. david.maltete@chu-rouen.fr
OBJECT: A collision/implantation or microlesion effect is commonly described
after subthalamic nucleus (STN) implantation for high-frequency stimulation, and
this is presumed to reflect disruption of cells and/or fibers. Off-period
dystonia, a frequent cause of disability in patients with advanced Parkinson
disease, can lead to the need for surgical treatment. The authors assessed the
early effect of this microlesion on off-period dystonia. METHODS: The authors
assessed 30 consecutive patients with the advanced levodopa-responsive form of
Parkinson disease. The patients' symptoms were Hoehn and Yahr Scale score > or =
3, the mean duration of their disease was 11.4 +/- 3.5 years, and they had
undergone bilateral implantation of electrodes within the STN for high-frequency
stimulation between February 2004 and December 2006. The microlesion effect was
defined by the clinical improvement (Unified Parkinson's Disease Rating Scale
[UPDRS] Part III score, UPDRS Part IV, item 35) assessed the morning of the 3rd
day following STN implantation, after at least a 12-hour withdrawal of
dopaminergic treatment and before the programmable pulse generator was switched
on (off-drug/off-stimulation mode). RESULTS: Compared with baseline (off state),
the microlesion effect improved the motor score (UPDRS Part III) by 27%.
Subscores for tremor, rigidity, and bradykinesia respectively improved by 42, 37,
and 25%. Nineteen patients (63%) suffered from off-period dystonia before
surgery. Twelve (41%) reported complete relief of their symptoms in the immediate
postoperative period and remained free of painful off-period dystonia throughout
the 6-month follow-up period. CONCLUSIONS: The author postulated that off-period
dystonia alleviation may reflect both a microsubthalamotomy and micropallidotomy
effect. They hypothesize, moreover, that the microlesion could play a role in the
6-month postoperative outcome.
PMID: 19877801 [PubMed - indexed for MEDLINE]
28. Ann Chir Plast Esthet. 2010 Jun;55(3):233-7. Epub 2009 Oct 28.
[Mondor's disease and breast plastic surgery]
[Article in French]
Dudrap E, Milliez PY, Auquit-Auckbur I, Bony-Rerolle S.
CHU Charles-Nicolle, Rouen, France. emmanueldudrap@yahoo.fr
<emmanueldudrap@yahoo.fr>
AIM: Mondor's disease is a rare complication following breast plastic surgery.
CASE REPORT: We report the case of a 40-year-old woman with breast shape and
volume asymmetry. She was treated by left breast submuscular prothesis
augmentation followed by right breast mastopexy 6 months later. Following this
surgery, she presented with subcutaneous painful abdominal cords on the right
side or Mondor's disease. DISCUSSION: We discuss the diagnosis, physiopathology
and treatment of this disease in the light of scientific literature. The
physiopathology is based on fascial origin in a context of local vascularitis.
CONCLUSION: Mondor's disease is a rare but benign pathology following breast
plastic surgery. The treatment is symptomatic and the surgeon must reassure the
patient on the benignity and the lack of consequence on the final cosmetic
result. 2009 Elsevier Masson SAS. All rights reserved.
PMID: 19875218 [PubMed - in process]
