1. Alzheimer Dis Assoc Disord. 2010 Dec 28. [Epub ahead of print]
Early Onset Dementia: Characteristics in a Large Cohort From Academic Memory
Clinics.
Picard C, Pasquier F, Martinaud O, Hannequin D, Godefroy O.
*Departments of Neurology of University Hospitals of Amiens †Laboratoire de
Neurosciences Fonctionnelles et Pathologies FRE3291 ‡Lille Nord de France, UDSL
EA 1046 and Rouen-CNR-MAJ and Inserm, France.
AIM: To describe the characteristics of early-onset dementia (EOD) in a cohort
from 3 memory clinics. METHODS: We assessed all patients with dementia referred
to the Academic Memory Clinics at Amiens, Lille, and Rouen University Medical
Centers between 2005 and 2007. Patients aged less than 65 years at the time of
onset of symptom were included in the EOD group, whereas older patients were
included in the late-onset dementia (LOD) group. RESULTS: Three thousand four
hundred and seventy-three patients (including 1932 women) were included and 811
(23.4%) were classified as EOD. The sex ratio was 1.12, whereas women were
overrepresented in LOD (P=0.001). Patients with EOD were more frequently
(P=0.001) living at home (87.3%), they had a lower educational level than the
general population (P=0.0001) but were more educated (P=0.001). The current Mini
Mental State Examination did not differ (P=0.3) between EOD (18.6±7.6) and LOD
(18.9±6). The most common causes of EOD were Alzheimer's (22.3%) and vascular
(15.9%) diseases and 4 pathologies that were significantly more frequent
(P=0.001) than in the LOD group: frontotemporal dementia (9.7%), alcohol-related
dementia (9.4%), traumatic brain injury (3.8%), and Huntington's disease (3%).
CONCLUSIONS: EOD is characterized by specific features and different causes
although Alzheimer's and vascular dementias remain the main causes of dementia in
EOD.
PMID: 21192236 [PubMed - as supplied by publisher]
2. Orthop Traumatol Surg Res. 2010 Dec 18. [Epub ahead of print]
Laxity measurements using stress radiography to assess anterior cruciate ligament
tears.
Beldame J, Bertiaux S, Roussignol X, Lefebvre B, Adam JM, Mouilhade F, Dujardin
F.
Orthopaedic Surgery and Traumatology Department, Rouen Teaching Medical Center,
1, rue de Germont, 76031 Rouen cedex, France.
INTRODUCTION: The clinical diagnosis of the anterior cruciate ligament (ACL) tear
is based on demonstrating anterior subluxation of the tibia on the femur. In any
of the following perspectives, diagnostic (cutoff value confirming rupture),
prognostic (treatment efficacy), and therapeutic (laxity influencing the
treatment), this laxity can be measured on stress X-rays. WORKING HYPOTHESIS: The
diagnostic value of dynamic radiographs is low for ACL rupture. Passive Telos(®)
X-rays have better diagnostic value, better radiologic quality, and are easier to
carry out than active Franklin-type X-rays. MATERIAL AND METHODS: A cohort of 112
patients (28 females, 84 males; mean age, 33.7 years [range, 18-72 years]) with
an indication for knee arthroscopy were studied prospectively. Before undergoing
the arthroscopic treatment, two series of images of both knees were taken: one
series of passive anterior drawer dynamic X-rays on a Telos(®) device at 250 N
and a series of active anterior drawer dynamic X-rays according to Franklin
(contraction of the quadriceps against 7 kg of weight at the ankle). The
arthroscopic evaluation of the ACL (reference status) was compared to the
anterior laxity measurements (absolute and differential) of each knee compartment
(medial, lateral, and average) to determine the diagnostic value of the two
radiological tests. RESULTS: We found 70 patients with an "arthroscopically
ruptured ACL", 32 with an "arthroscopically healthy ACL", and 10 with a "partial
rupture". The measurement of the anterior drawer values on the dynamic X-rays
(active and passive) by two independent observers was reliable and reproducible
(ICC>0.80), particularly when using the medial compartment (ICC=0.96) and the
differential values eliminating the interobserver measurement error and
interindividual laxity variations. In terms of X-ray technique, the active images
were more frequently painful and the radiographic result showed less good quality
than the Telos images. The anterior drawer values in the "healthy ACL" group were
significantly less than in the "ruptured ACL" group for the Telos(®) images,
whether the measurements were absolute or differential. For the Franklin images,
this difference was only significant for the absolute values. Used for diagnosis
(4-mm differential on the medial compartment), the passive dynamic images had
lower diagnostic values (Se=59% and Sp=90%) than the series reported in the
literature, which were marked by great heterogeneity. CONCLUSION: The measurement
of anterior drawer values on Telos(®) and Franklin dynamic X-rays is a reliable
and reproducible measurement, particularly when using the medial compartment and
differential measurements. This small series did not demonstrate a diagnostic
value for the Franklin images, contrary to the Telos(®) X-rays. Used for
diagnostic purposes, the Telos(®) images had a low sensitivity; consequently,
they should be used preferentially for prognostic or therapeutic purposes. LEVEL
OF EVIDENCE: Level III, prospective case-control study.
PMID: 21169080 [PubMed - as supplied by publisher]
3. Neurobiol Dis. 2010 Dec 16. [Epub ahead of print]
Efficiency of laryngeal motor nerve repair is greater with bulbar than with
mucosal olfactory ensheathing cells.
Paviot A, Guérout N, Bon-Mardion N, Duclos C, Jean L, 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; Otorhinolaryngology, Head and
Neck Surgery Department, Rouen University Hospital, Charles Nicolle hospital, 1
rue de Germont, 76031 Rouen, France.
The real ability of OECs provided by olfactory mucosa cultures (OM-OECs) and
those from olfactory bulb cultures (OB-OECs) must be better characterized in
order to propose their future clinical application. Therefore, we used a lesion
of the vagus nerve (VN), which constitutes a severe motor denervation due to long
distance of the muscular targets (4.5cm). We performed a section/anastomosis
surgery of the VN, at the third tracheal ring. Then, OM-OECs and OB-OECs were
injected in matrigel around the lesion site. Three months after surgery,
laryngeal muscle activity, synkinesis phenomena and latency were evaluated by
videolaryngoscopy and electromyography recordings. To complete these procedures,
axonal morphometric study of the right recurrent nerve was performed to assess
axonal regrowth and tracking of green fluorescent protein positive cells was
performed. Recurrent nerve is the motor branch innervating the laryngeal muscles,
and is located distally to the lesion, near the muscular targets (0.7cm). These
analyses permitted to compare the ability of these two populations to improve
functional recovery and axonal regrowth. Our results show that, OM-OECs improved
electrical muscular activity and nervous conduction with significant tissue
healing but induced aberrant movement and poor functional recovery. In contrast,
OB-OECs induced a partial functional recovery associated with an increase in the
number of myelinated fibers and nervous conduction. Our study suggests that, as
recently reported in a microarray study, OM-OECs and OB-OECs express different
properties. In particular, OM-OECs could regulate inflammation processes and
extracellular matrix formation but have a poor regeneration potential, whereas,
OB-OECs could improve functional recovery by inducing targeted axonal regrowth.
PMID: 21168497 [PubMed - as supplied by publisher]
4. Fertil Steril. 2010 Dec 16. [Epub ahead of print]
Vaporization of ovarian endometrioma using plasma energy: histologic findings of
a pilot study.
Roman H, Pura I, Tarta O, Mokdad C, Auber M, Bourdel N, Marpeau L, Sabourin JC.
Department of Gynecology and Obstetrics, Rouen University Hospital, Rouen,
France; Research Group "Spermatogenesis and Male Gamete Quality," Rouen
University Hospital, Rouen, France.
In ten ovarian endometriomas of diameter exceeding 30 mm, managed by complete
vaporization of the inner surface using plasma energy followed by cystectomy, we
performed histologic evaluation of the depth of necrosis and the effectiveness of
endometrial tissue ablation. We observed that plasma energy allows the ablation
of endometrial tissue with minimal damage to the ovarian parenchyma, which
suggests that this technique might be of particular interest for women with risk
factors of postoperative ovarian reserve impairment, such as recurrent and
bilateral endometriomas.
PMID: 21168130 [PubMed - as supplied by publisher]
5. Neurogastroenterol Motil. 2010 Dec 19. doi: 10.1111/j.1365-2982.2010.01647.x.
[Epub ahead of print]
Involvement of the aero-digestive tract in swallowing-ventilation coordination:
an animal study.
Ouahchi Y, Bon-Mardion N, Marie JP, Verin E.
Experimental Surgery Laboratory, Rouen University, Rouen, France
Otorhinolaryngology and Head and Neck Surgery Department, Rouen University
Hospital, Rouen, France Physiology Department, Rouen University Hospital, Rouen,
France.
Background The precise coordination of swallowing and ventilation is considered
an important mechanism for minimizing the risk of pulmonary aspiration. The aim
of this study was to test the hypothesis that the aero-digestive tract is
involved in swallowing-ventilation coordination in rats. Methods The goal of the
first part of the study was to characterize swallowing events associated with
ventilation signals obtained using a barometric plethysmograph. This was done in
seven rats with the help of esophageal electromyograms. Thereafter,
swallowing-ventilation coordination was assessed in 15 rats with right unilateral
vocal cord paralysis and 10 rats following oropharyngeal anesthesia. Key Results
In healthy animals, 92 ± 11% of swallows occurred during expiration and 8 ± 11%
during inspiration. Swallow frequency and swallowing characteristics based on
ventilation did not change following unilateral laryngeal paralysis. Swallows
during expiration decreased (71 ± 9%, P < 0.01) while swallows during inspiration
increased (29 ± 11%, P < 0.01) following oropharyngeal anesthesia with lidocaine.
Conclusions & Inferences Our findings using a rat model need to be confirmed,
however, they indicated that a rat model can be used to study oropharyngeal
dysphagia and that laryngo-pharyngeal anesthesia alters swallowing-ventilation
coordination.
PMID: 21166961 [PubMed - as supplied by publisher]
6. J Acquir Immune Defic Syndr. 2010 Dec 15. [Epub ahead of print]
Comparative RNA quantification of HIV-1 group M and non-M with the Roche Cobas
AmpliPrep/Cobas TaqMan HIV-1 v2.0 and Abbott Real Time HIV-1 PCR assays.
Sire JM, Vray M, Merzouk M, Plantier JC, Pavie J, Maylin S, Timsit J,
Lascoux-Combe C, Molina JM, Simon F, Delaugerre C.
1Laboratoire de Virologie, Hôpital Saint-Louis AP-HP, INSERM U941, Université
Paris-Diderot, Paris, France; 2Unité d'Epidémiologie des Maladies Emergentes,
Institut Pasteur, Paris, France; 3Laboratoire de Virologie, Centre Hospitalier
Universitaire Charles Nicolle, Faculté de Médecine et de Pharmacie, Rouen,
France; 4Service des Maladies Infectieuses et Tropicales, Hôpital Saint-Louis,
Université Paris-Diderot Paris, France; 5Service des Maladies Sexuellement
Transmissibles, Hôpital Saint-Louis, Paris, France; and 6Service de Médecine
Interne, Hôpital Saint-Louis, Université Paris-Diderot, Paris, France.
BACKGROUND:: A new version of the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 assay
(CA/CTM v2.0) has been introduced to overcome the under-quantification observed
with the first version. METHODS:: We compared the Roche Cobas CA/CTM v2.0 and
Abbott RealTime HIV-1 assays for HIV-1 group M and non-M viral load measurement.
RESULTS:: We found a good correlation (r=0.96) between the two techniques for the
260 HIV-1 group M plasma samples tested. The Roche Cobas assay gave significantly
higher values than the Abbott assay, and 51 samples (20%) yielded differences
greater than 0.5 log10 copies/mL. Conversely, two samples were more than 0.5
log10 copies/mL higher with the Abbott assay than with the Roche Cobas assay.
Among the 84 samples with undetectable VL in the Abbott assay (detection limit 40
copies/mL), 17 (20%) were detectable with the CA/CTM v2.0 assay (detection limit
20 copies/mL), with values ranging from 41 to 897 copies/mL. Extrapolation of the
Abbott curves led to 10/17 (59%) of these samples being quantifiable. HIV-1
groups O and P were similarly quantified by the two techniques. CONCLUSION:: The
results of the Roche Cobas CA/CTM v2.0 and Abbott RealTime HIV-1 assays correlate
well. The new version of the CA/CTM assay shows improved sensitivity.
Nevertheless, the two assays differ by more than 0.5 log10 copies/mL for some
samples.
PMID: 21164353 [PubMed - as supplied by publisher]
7. Clin Neuropharmacol. 2010 Dec 14. [Epub ahead of print]
Erythrocytes Catechol-O-Methyl Transferase Activity Is Up-Regulated After a
3-Month Treatment by Entacapone in Parkinsonian Patients.
Maltête D, Cottard AM, Mihout B, Costentin J.
*Department of Neurology, and †Unit of Clinical Neurobiology, Rouen University
Hospital, Rouen, France.
OBJECTIVES:: Entacapone is a highly potent, reversible, peripherally acting
catechol-O-methyl transferase (COMT) inhibitor that is used as an adjunct to
L-dopa in the treatment of patients with Parkinson disease (PD). Nevertheless,
the consequence of the long-lasting inhibition of COMT by entacapone has never
been investigated. We assessed the variation of the soluble red blood cell
(S-RBC)-COMT activity after 3 months of chronic treatment by entacapone.
METHODS:: Twelve consecutive white PD patients (3 women and 9 men; mean age, 65.7
± 2.4 years) with l-dopa-related motor fluctuations were assessed. Entacapone 200
mg was given in combination with each scheduled l-dopa/dopa decarboxylase
inhibitor dose (range, 3-5 doses daily). The S-RBC-COMT activity was determined
both before entacapone administration (baseline) and twice, respectively, after 1
and 3 months treatment with entacapone, that is, on morning, after at least a
12-hour withdrawal of entacapone and l-dopa and before the following first daily
administration. RESULTS:: Mean baseline S-RBC-COMT activity was 0.72 ± 0.09
pmol/min per milligram (range, 0.30-1.29 pmol/min per milligram) of protein.
After 3 months, the level increased significantly in all PD patients from 0.72 ±
0.09 pmol/min per milligram (range, 0.30-1.29 pmol/min per milligram) to 1.19 ±
0.13 pmol/min per milligram (range, 0.58-2.14 pmol/min per milligram) of protein
(P < 0.01), which corresponds to a mean increase of 72.9 ± 9.2% (range,
24%-146%). CONCLUSIONS:: Our findings suggest that a long-lasting inhibition of
the COMT may limit the efficacy of entacapone by development of a tolerance.
Moreover, one may assume that an abrupt withdrawal of the treatment will be
followed by a dramatic worsening of motor disability.
PMID: 21164341 [PubMed - as supplied by publisher]
8. Rev Mal Respir. 2010 Dec;27(10):1132-4.
[For a best management of patients with severe hemoptysis].
[Article in French]
Lamia B, Clavier E, Girault C.
PMID: 21163391 [PubMed - in process]
9. Joint Bone Spine. 2010 Dec 8. [Epub ahead of print]
AL amyloidosis with myeloma mimicking rheumatoid arthritis.
Roca F, Lanfant-Weybel K, Vittecoq O, Goëb V.
Service de rhumatologie, hôpitaux de Rouen, CHU de Rouen, Rouen, France.
PMID: 21145774 [PubMed - as supplied by publisher]
10. Diabetes Metab. 2010 Dec 6. [Epub ahead of print]
Structural modifications in the arterial wall during physiological aging and as a
result of diabetes mellitus in a mouse model: Are the changes comparable?
Prévost G, Bulckaen H, Gaxatte C, Boulanger E, Béraud G, Creusy C, Puisieux F,
Fontaine P.
Laboratory for the Biology of Vascular Aging, School of Medicine, University
Hospital of Lille, Lille, France; Endocrinology Department, University Hospital
of Rouen, Rouen, France.
AIM: Vascular accelerated aging represents the major cause of morbidity and
mortality in subjects with diabetes mellitus. In the present study, our aim was
to compare premature functional and morphological changes in the arterial wall
resulting from streptozotocin (STZ)-induced diabetes mellitus in mice over a
short-term period with those that develop during physiological aging. The effect
of aminoguanidine (AG) on the prevention of these alterations in the diabetic
group was also analyzed. METHODS: The vascular relaxation response to
acetylcholine (ACh) in the mouse was tested in isolated segments of phenylephrine
(Phe)-precontracted aorta at 2, 4 and 8 weeks (wk) of STZ-induced diabetes and
compare to 12- and 84-wk-old mice. Aortic structural changes were investigated,
and receptor for AGE (RAGE) aortic expression was quantified by western blot.
RESULTS: Compared to the 12-wk control group (76±5%), significant
endothelium-dependant relaxation (EDR) impairment was found in the group of
12-wk-old mice, which underwent a 4-wk diabetes-inducing STZ treatment (12wk-4WD)
(52±4%; P<0.01) and was yet more apparent in the group of 16-wk-old mice, which
underwent an 8-wk diabetes-inducing STZ treatment (16wk-8WD) (34±4%; P<0.001).
The alteration in EDR was relatively comparable between the diabetic 12wk-4WD
group and the 84-wk-old group (52.7±4 vs. 48±4%). Intima/media aortic thickening
and aortic structural changes were significantly increased in the diabetic
12wk-4WD group and were even more apparent in the 84-wk group compared to the
12-wk controls. AG treatment in the 12wk-4WD+AG diabetic group significantly
improved EDR, decreased RAGE expression and showed an aging preventive effect on
the structural changes of the arterial wall. CONCLUSION: Our study compared EDR
linked to physiological aging with that observed in the case of STZ-induced
diabetes over a short-term period, and demonstrated the beneficial effect of AG.
PMID: 21144786 [PubMed - as supplied by publisher]
11. Br J Cancer. 2010 Dec 7;103(12):1765-72. Epub 2010 Nov 23.
Molecular determinants of anti-EGFR sensitivity and resistance in metastatic
colorectal cancer.
Di Fiore F, Sesboüé R, Michel P, Sabourin JC, Frebourg T.
Faculty of Medicine, Institute for Biomedical Research, 22 Boulevard Gambetta,
76183 Rouen, France. frederic.di-fiore@chu-rouen.fr
Since 2004, the clinical impact of monoclonal antibodies (mAbs) targeting the
epidermal growth factor receptor (EGFR) on patients with metastatic colorectal
cancer (MCRC) has been clearly established. The combination of these biological
agents with conventional chemotherapy has led to a significant improvement in
response rate, progression-free survival and overall survival in first-line as
well as in second- or third-line treatment of MCRC. However, the high variability
of response and outcome in MCRC patients treated with these anti-EGFR mAbs has
highlighted the need of identifying clinical and/or molecular predictive markers
to ensure appropriate use of targeted therapies. The presence of somatic KRAS
mutations has been clearly identified as a predictive marker of resistance to
anti-EGFR in MCRC, and the use of anti-EGFR mAbs is now restricted to patients
with no detectable KRAS mutation. Several studies have indicated that
amplification of EGFR, overexpression of the EGFR ligands and inactivation of the
anti-oncogene TP53 are associated with sensitivity to anti-EGFR mAbs, whereas
mutations of BRAF and PIK3CA and loss of PTEN expression are associated with
resistance. Besides these somatic variations, germline polymorphisms such as
those affecting genes involved in the EGFR pathway or within the immunoglobulin
receptors may also modulate response to anti-EGFR mAbs. Until now, all these
markers are not completely validated and only KRAS genotyping is mandatory in
routine practice for use of the anti-EGFR mAbs in MCRC.
PMID: 21139621 [PubMed - in process]
12. Hum Reprod. 2010 Dec 2. [Epub ahead of print]
Surgical management of deep infiltrating endometriosis of the rectum: pleading
for a symptom-guided approach.
Roman H, Vassilieff M, Gourcerol G, Savoye G, Leroi AM, Marpeau L, Michot F,
Tuech JJ.
Department of Gynecology and Obstetrics, Clinique Gynécologique et Obstétricale,
Rouen University Hospital, 1 rue de Germont, 76031 Rouen, France.
Two surgical approaches are usually employed in the treatment of deep
infiltrating endometriosis of the rectum (DIER): colorectal resection removing
the rectal segment affected by the disease, and nodule excision either without
opening the rectum (shaving) or by removing the nodule along with the surrounding
rectal wall (full thickness or disc excision). Although the present available
data are from retrospective series reported by surgeons who generally perform
only one technique, there is no evidence to support the risk of recurrences as a
valid argument in favour of colorectal resection over rectal nodule excision. The
advantage of a lower morbidity associated with nodule excision is not necessarily
at the cost of an increased rate of pain recurrences, especially in women
benefiting from post-operative medical treatment. The symptom-guided surgical
approach in DIER primarily focuses on the relief of digestive symptoms and pelvic
pains, rather than on mandatory 'carcinologic' resection of lesions. In addition,
the risk of new post-operative unpleasant symptoms as a result of a compulsory
and systematic excision of all endometriotic foci may be avoided. In a majority
of cases, pelvic anatomy and digestive function can be restored by shaving or
disc excision, as well as by colorectal resection; thus digestive complaints can
be resolved even when the rectum is conserved. The most accurate evaluation of
the results of DIER surgery should be provided by post-operative evolution in
digestive function. Even though qualityoflife is improved for the majority of
patients managed by colorectal resection, the question is whether or not a
greater health improvement can be achieved by performing nodule excision, which
avoids various post-operative and functional digestive complications. In
addition, continuous medical treatment leads to a decrease in endometriotic
nodules and prevents post-operative pain recurrences. Instead of choosing between
medical and surgical management in the treatment of DIER, it is most likely that
the two therapies should be associated.
PMID: 21131296 [PubMed - as supplied by publisher]
13. Physiol Behav. 2010 Dec 2;101(5):639-48. Epub 2010 Sep 29.
Chemotherapy-induced anorexia is accompanied by activation of brain pathways
signaling dehydration.
Sinno MH, Coquerel Q, Boukhettala N, Coëffier M, Gallas S, Terashi M, Ibrahim A,
Breuillé D, Déchelotte P, Fetissov SO.
Digestive System & Nutrition Laboratory (ADEN EA4311), Rouen University, IFR23,
Rouen 76183, France.
BACKGROUND AND AIMS: Cancer chemotherapy is accompanied by anorexia and
mucositis. To clarify the mechanisms of chemotherapy-induced anorexia, we studied
the expression of c-fos and appetite-regulating neuropeptidergic and inflammatory
mediators in the hypothalamus of rats treated with methotrexate (MTX).
METHODS: Sprague-Dawley rats received MTX (2.5mg/kg, subcutaneously) on three
consecutive days and were compared with ad libitum- and pair-fed control rats
five days after the first injection.
RESULTS: MTX administration inhibited food and water intake and induced lean and
fat mass losses. MTX also induced mucositis and diarrhea without changes in
plasma osmolality. Pair-fed rats lost a similar amount of body weight but had no
mucositis or diarrhea. Increased number of c-fos positive hypothalamic
vasopressin neurosecretory neurons as well as numerous c-fos positive cells in
the subfornical organ and in the organum vasculosum of the lamina terminalis were
found in MTX-treated as compared to control or pair-fed rats. In both MTX and
pair-fed rats, a decrease of hypothalamic proopiomelanocortin mRNA expression and
low plasma levels of interleukin-1β (IL-1β) were found reflecting probably the
energy deficit. No significant changes of IL-1β mRNA expression and intensity of
microglial staining in the hypothalamus were found in MTX-treated rats.
CONCLUSION: The pattern of c-fos expression in the hypothalamus during MTX
treatment is similar to that seen with systemic dehydration, which is known to
cause anorexia. No evidence of inflammatory origin of anorexia was found,
suggesting that chemotherapy accompanied by mucositis and diarrhea may cause
anorexia associated with systemic dehydration.
PMID: 20883707 [PubMed - in process]
14. Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2562-7. Epub 2010 Sep 16.
Endothelial estrogen receptor {alpha} plays an essential role in the coronary and
myocardial protective effects of estradiol in ischemia/reperfusion.
Favre J, Gao J, Henry JP, Remy-Jouet I, Fourquaux I, Billon-Gales A, Thuillez C,
Arnal JF, Lenfant F, Richard V.
Department of Pharmacology, Institut National de la Santé et de la Recherche
Médicale U644 and Rouen University Hospital, Institute for Biomedical Research
Institut Fédératif de Recherches, University of Rouen, France.
OBJECTIVE: To assess the coronary endothelial protective effects of 17β-estradiol
(E2) and the role of estrogen receptor (ER) α in ischemia/reperfusion (I/R).
METHODS AND RESULTS: E2 exerts protective effects in cardiac I/R. However, the
implication in vivo of the endothelium and the cellular targets of the
anti-ischemic effects of E2 are unknown. Mice were subjected to I/R (30 minutes
of I and 1 hour of R) in vivo, after which acetylcholine-induced relaxation of
isolated coronary segments was assessed ex vivo. I/R induced a coronary
endothelial dysfunction in untreated ovariectomized mice that was prevented by
long-term treatment with E2 in wild-type, but not in ERα(-/-), mice. Chimeric
mice inactivated for ERα in the hematopoietic compartment remained protected by
E2. Further inactivation of endothelial ERα abolished the protective action of E2
on coronary endothelial function in Tie2-Cre(+) ERα(f/f) mice. More importantly,
E2 significantly limited infarct size in wild-type mice but not in mice deficient
in endothelial ERα, even in the presence of hematopoietic ERα.
CONCLUSIONS: Endothelial ERα plays a crucial role in the E2-induced prevention of
endothelial dysfunction after I/R. To our knowledge, we demonstrate for the first
time, by using unique genetically modified mice, that targeting endothelial
protection per se can confer cardiomyocyte protection in I/R.
PMID: 20847304 [PubMed - indexed for MEDLINE]
15. Cell Mol Biol Lett. 2010 Dec;15(4):600-10. Epub 2010 Aug 28.
TRPC expression in mesenchymal stem cells.
Torossian F, Bisson A, Vannier JP, Boyer O, Lamacz M.
IFRMP, Institute for Biomedical Research, Inserm, U, University of Rouen, France.
Transient receptor potential canonical (TRPC) channels are key players in calcium
homeostasis and various regulatory processes in cell biology. Little is currently
known about the TRPC subfamily members in mesenchymal stem cells (MSC), where
they could play a role in cell proliferation. We report on the presence of TRPC1,
2, 4 and 6 mRNAs in MSC. Western blot and immunofluorescence staining indicate a
membrane and intracellular distribution of TRPC1. Furthermore, the decrease in
the level of TRPC1 protein caused by RNA interference is accompanied by the
downregulation of cell proliferation. These results indicate that MSC express
TRPC1, 2, 4 and 6 mRNA and that TRPC1 may play a role in stem cell proliferation.
PMID: 20803258 [PubMed - in process]
16. Arthritis Care Res (Hoboken). 2010 Dec;62(12):1739-47. doi: 10.1002/acr.20321.
Serum IgA rheumatoid factor and pyridinoline in very early arthritis as
predictors of erosion(s) at two years: a simple model of prediction from a
conservatively treated community-based inception cohort.
Le Loët X, Brazier M, Mejjad O, Boumier P, Daragon A, Gayet A, Pouplin S, Tron F,
Zarnitsky C, Vittecoq O, Menard JF, Fardellone P.
INSERM Unit 905 and Rouen University Hospital, Rouen, France.
xavier.le-loet@chu-rouen.fr
OBJECTIVE: To identify, in conservatively treated, very early arthritis patients,
predictors of ≥1 erosion(s) at 2 years, and to construct a prediction model.
METHODS: Community-based adults (n=310) who had never taken disease-modifying
antirheumatic drugs (DMARDs) or steroids with swelling of ≥2 joints persisting
for >4 weeks and lasting <6 months were recruited. Erosion status was assessed at
0, 6, 12, and 24 months; evaluations were comprised of clinical criteria (Disease
Activity Score, Health Assessment Questionnaire), C-reactive protein level,
erythrocyte sedimentation rate, autoantibodies, bone and cartilage markers, hand
densitometry, and HLA class II shared epitopes. Patients meeting American College
of Rheumatology rheumatoid arthritis (RA) criteria or with undifferentiated
arthritis (UA) were followed and treated conservatively: one-third of RA patients
and three-fourths of UA patients received no DMARDs during 2 years; a biologic
agent was given to 1.8% of the patients during the first year. The main judgment
criterion was ≥1 erosion(s) at 2 years.
RESULTS: At 2 years, 219 patients were assessed; 31.3% with RA and 10.6% with UA
had ≥1 erosion(s). Logistic regression analysis at that time showed erosion(s)
strongly associated with serum IgA rheumatoid factor (IgA-RF) and pyridinoline
levels for the 190 patients with no baseline erosions, with the corresponding
receiver operating characteristic curve having an area under the curve of 0.77
(95% confidence interval 0.64-0.86). A prediction model was constructed with
IgA-RF thresholds of 5 and 25 IU/ml and a pyridinoline threshold of 10 nM/liter;
odds ratios ranged from 1 for IgA-RF<5 IU/ml and pyridinoline <10 nM/liter to
50.75 for the association of IgA-RF≥5 IU/ml and pyridinoline≥10 nM/liter.
CONCLUSION: This model, using serum IgA-RF and pyridinoline concentrations, was
able to predict≥1 erosion(s) at 2 years in very early arthritis patients.
PMID: 20740612 [PubMed - in process]
17. Arthritis Care Res (Hoboken). 2010 Dec;62(12):1748-55. doi: 10.1002/acr.20325.
Intravenous immunoglobulins for steroid-refractory esophageal involvement related
to polymyositis and dermatomyositis: a series of 73 patients.
Marie I, Menard JF, Hatron PY, Hachulla E, Mouthon L, Tiev K, Ducrotte P, Cherin
P.
Centre Hospitalier Universitaire Rouen, and INSERM U 905, University of Rouen
IFRMP, Institute for Biochemical Research, Rouen, France.
isabelle.marie@chu-rouen.fr
OBJECTIVE: To assess the long-term outcome of esophageal complications in the
group of patients receiving intravenous immunoglobulins (IVIG) for the treatment
of severe steroid-refractory esophageal involvement related to
polymyositis/dermatomyositis (PM/DM).
METHODS: We retrospectively reviewed the medical records of 73 patients (39 with
PM, 34 with DM) with steroid-resistant esophageal involvement. Esophageal
involvement was evaluated by clinical and manometric investigations.
RESULTS: Seventy-three patients with steroid-refractory esophageal involvement
related to PM/DM received IVIG therapy (2 gm/kg monthly). The median interval
between PM/DM diagnosis and the onset of esophageal complications was 6 months.
The most common clinical manifestations revealing esophageal dysfunction were
dysphagia (69.9%), coughing while eating (61.6%), and gastroesophageal reflux
into the pharynx and/or mouth (34.2%). Twenty-five patients exhibited
life-threatening esophageal complications requiring exclusive enteral feeding; 33
patients (45.2%) with esophageal impairment developed aspiration pneumonia. Sixty
patients (82.2%) exhibited resolution of esophageal clinical manifestations,
leading to a return to normal oral feeding and ablation of feeding enteral tubes.
Four other patients (5.5%) improved, although they still experienced mild
dysphagia intermittently. Because of impaired cricopharyngeal muscle relaxation,
another patient successfully underwent cricopharyngeal myotomy. Eight patients
died from aspiration pneumonia (n=6) and cancer (n=2). Muscle weakness, thoracic
myopathy, and aspiration pneumonia were independent predictive factors of
IVIG-treated esophageal complications in PM/DM patients.
CONCLUSION: Our findings indicate that IVIG should be considered in
life-threatening esophageal impairment complicating steroid-resistant PM/DM. We
also suggest that combined therapy of IVIG and high-dose steroids may be the
first-line therapy in PM/DM patients with life-threatening esophageal
manifestations.
PMID: 20722047 [PubMed - in process]
18. Haematologica. 2010 Dec;95(12):2031-7. Epub 2010 Aug 16.
Immunoassay for human serum hemojuvelin.
Brasse-Lagnel C, Poli M, Lesueur C, Grandchamp B, Lavoinne A, Beaumont C, Bekri
S.
Laboratoire de Biochimie Médicale, Hôpital Universitaire de Rouen, EA4309
Endothélium Microvasculaire et Lésions Cérébrales Néonatales, Université de
Rouen, Rouen, France. carole.lagnel@univ-rouen.fr
Comment in:
Haematologica. 2010 Dec;95(12):1989-91.
BACKGROUND: Hemojuvelin, a critical regulator of iron homeostasis, is involved in
the regulation of hepcidin expression and iron homeostasis. It is expressed both
as a membrane-bound form and as a soluble one. Serum hemojuvelin can be produced
by secretion following furin cleavage or by proteolytic cleavage of the
membrane-bound form by matriptase 2 (TMPRSS6). These forms contribute to
down-regulation of hepcidin expression upon iron deficiency or hypoxia. This
study describes the development and validation of the first enzyme-linked
immunosorbent assay for hemojuvelin in human serum.
DESIGN AND METHODS: This assay is based on the use of a recombinant human
repulsive guidance molecule-c peptide and a polyclonal antibody against
hemojuvelin able to recognize the recombinant peptide and the native soluble
hemojuvelin by immunoprecipitation.
RESULTS: The enzyme-linked immunosorbent assay was validated and appeared to be a
robust method with intra- and inter-coefficients of variance ranging from 2.6% to
15%. The assay was able to quantify hemojuvelin levels in a control population
within a range from 0.88 to 1.14 mg/L. Patients with iron-refractory
iron-deficiency anemia with a mutation in the TMPRSS6 gene were found to have
lower levels of circulating hemojuvelin than those in healthy patients. The
enzyme-linked immunosorbent assay also showed that soluble hemojuvelin levels
were significantly higher in patients with anemia of chronic disease than in
control individuals.
CONCLUSIONS: This enzyme-linked immunosorbent assay has a good specificity and
sensitivity for the quantification of soluble hemojuvelin in human serum and
could be a valuable aid to understanding the physiological role of this protein.
PMCID: PMC2995560
PMID: 20713458 [PubMed - in process]
19. Med Mal Infect. 2010 Dec;40(12):669-676. Epub 2010 Jun 19.
[Specific diagnosis and follow-up of HIV-1 group O infection: RES-O data.]
[Article in French]
Depatureaux A, Leoz M, De Oliveira F, Gueudin M, Damond F, Descamps D,
Brun-Vézinet F, Lemée V, Simon F, Barin F, Plantier JC.
Laboratoire associé au CNR du VIH, EA 2656, CHU Charles-Nicolle, 76031 Rouen,
France.
INTRODUCTION: HIV-1 group O (HIV-O), mainly found in Cameroon, has a very high
genetic diversity with consequences on the diagnosis and treatment of patients,
requiring the development of specific tools. OBJECTIVE: We present the currently
available tools for the specific detection of HIV-O and its therapeutic
monitoring, and the first RES-O data, a French network for the identification and
monitoring of patients infected by HIV-O. METHOD: The diagnosis of infection was
confirmed by group-specific envelope serotyping. The viral load was assessed by a
specific technique, LTR-O, developed in the laboratory and compared to the
nonspecific kit RealTime HIV-1 (Abbott). The sequencing of antiretroviral target
regions (Protease, Reverse Transcriptase (RT), Integrase and Gp41), was performed
by specific primers. The analysis of resistance mutations was performed with the
ANRS algorithm used for HIV-M. RESULTS: HIV-O infection was confirmed for 117
patients. Measuring viral load showed the two techniques were equivalent, but
with a tendency to under-quantification for the Abbott technique greater than 1
log for 5% of samples. 70 to 100% of the studied strains had at least 10
mutations in the Protease, four4 in the RT, and one in Gp41, resulting in a
natural genotypic resistance to some anti-retroviral molecules. DISCUSSION: The
diagnosis and monitoring of HIV-O infection is now possible. However, the impact
of this variant's natural polymorphism on response to treatment remains
undocumented.
PMID: 20646884 [PubMed - as supplied by publisher]
20. Rev Med Interne. 2010 Dec;31(12):865-6. Epub 2010 Jun 3.
[Perineal erythema].
[Article in French]
Becourt C, Girszyn N, Prevost G, Janvresse A, Marie I.
Département de médecine interne, CHU Rouen-Boisguillaume, 1, rue de Germont,
76031 Rouen cedex, France.
PMID: 20605279 [PubMed - in process]
21. Dysphagia. 2010 Dec;25(4):291-7. Epub 2009 Oct 24.
Sensory transcutaneous electrical stimulation improves post-stroke dysphagic
patients.
Gallas S, Marie JP, Leroi AM, Verin E.
Service de physiologie digestive, urinaire, respiratoire et sportive, CHU de
Rouen, 1 rue de Germont, 76031, Rouen Cedex, France.
Oropharyngeal dysphagia is frequent in stroke patients and increases mortality,
mainly because of pulmonary complications. We hypothesized that sensitive
transcutaneous electrical stimulation applied submentally during swallowing could
help rehabilitate post-stroke oropharyngeal dysphagia by improving cortical
sensory motor circuits. Eleven patients were recruited for the study (5 females,
68 ± 11 years). They all suffered from recent oropharyngeal dysphagia (>eight
weeks) induced by a hemispheric (n = 7) or brainstem (n = 4) stroke, with
pharyngeal residue and/or laryngeal aspiration diagnosed by videofluoroscopy.
Submental electrical stimulations were performed for 1 h every day for 5 days
(electrical trains: 5 s every minute, 80 Hz, under motor threshold). During the
electrical stimulations, the patients were asked to swallow one teaspoon of paste
or liquid. Swallowing was evaluated before and after the week of stimulations
using a dysphagia handicap index questionnaire, videofluoroscopy, and cortical
mapping of pharyngeal muscles. The results of the questionnaire showed that
oropharyngeal dysphagia symptoms had improved (p < 0.05), while the
videofluoroscopy measurements showed that laryngeal aspiration (p < 0.05) and
pharyngeal residue (p < 0.05) had decreased and that swallowing reaction time
(p < 0.05) had improved. In addition, oropharyngeal transit time, pharyngeal
transit time, laryngeal closure duration, and cortical pharyngeal muscle mapping
after the task had not changed. These results indicated that sensitive submental
electrical stimulations during swallowing tasks could help to rehabilitate
post-stroke swallowing dysphagia by improving swallowing coordination. Plasticity
of the sensory swallowing cortex is suspected.
PMID: 19856025 [PubMed - in process]
