1: Hypertension 2001 Dec 1;38(6):1446-50
Chronic ACE Inhibition Enhances the Endothelial Control of Arterial Mechanics
and Flow-Dependent Vasodilatation in Heart Failure.
Joannides R, Bizet-Nafeh C, Costentin A, Iacob M, Derumeaux G, Cribier A,
Thuillez C.
Departments of Pharmacology (R.J., A.C., M.I., C.T.) and Cardiology (C.B.-N.,
G.D., A.C.), INSERM E9920, IFRMP 23, Rouen University Hospital, Rouen, France.
Reduced conduit arteries flow-dependent dilatation and altered compliance have
been described during heart failure. However, the role of shear stress, the
relation between endothelial dysfunction and mechanics, and the effect of
chronic ACE inhibition on this relationship have not been investigated. The
present study was designed to evaluate in heart failure patients the
relationship between flow-dependent dilatation and radial artery mechanics at
known shear stress levels and to assess the effect of chronic ACE inhibition.
Sixteen stable congestive heart failure patients, who had never been treated
with ACE inhibitors, participated in the study. Arterial pressure, cardiac
output (bioimpedance), radial artery diameter (echo tracking) and flow
(Doppler), total blood viscosity, and mean artery wall shear stress were
assessed before and during a gradual increase in the forearm blood flow in
response to gradual distal hand skin heating. Cross-sectional radial artery
compliance and distensibility indexes were calculated at 34 degrees C, 40
degrees C, and 44 degrees C. The endothelium-independent vasodilatation was
evaluated by use of glyceryl trinitrate. All parameters were assessed before and
24 hours after the last administration of perindopril (4 mg once daily) or
placebo in a 2-month double-blind randomized study. Before treatment, there was
no difference between the 2 groups for all parameters. After chronic ACE
inhibition, systolic arterial pressure decreased at baseline from 12611 to
11810 mm Hg (P<0.05). During heating, the increase in diameter in response to
shear stress was higher after ACE inhibition than after placebo (time/treatment
interaction, P<0.05). Moreover, in contrast to placebo, at the same shear
stress, there was a significant increase in compliance (3.230.79x10(-7) to
6.822.47x10(-7) m(2)/kPa, P<0.05) and distensibility (5.711.35x10(-3) to
8.871.88x10(-3)/kPa, P<0.05) during heating after ACE inhibition. The effect
of glyceryl trinitrate did not change. The present study demonstrates that
chronic administration of the ACE inhibitor perindopril increases the magnitude
of the flow-dependent dilatation and restores the flow-dependent increase in
compliance and distensibility of the radial artery evaluated at stable shear
stress. In addition, the decrease in baseline systolic arterial pressure after
ACE inhibitor suggests an associated increase in the distensibility of the
proximal elastic conduit arteries.
PMID: 11751733 [PubMed - in process]
2: Arch Phys Med Rehabil 2001 Dec;82(12):1705-11
Pelvic and lower limb compensatory actions of subjects in an early stage of hip
osteoarthritis.
Watelain E, Dujardin F, Babier F, Dubois D, Allard P.
Laboratoire d'Analyse du Mouvement, Service d'Exploration Neurophysiologique
Hopital Roger Salengro, Centre Hospitalier Regional Universitaire (CHRU), Lille,
France. eric.watelain@univ-valenciennes.fr
OBJECTIVE: To determine if compensatory actions take place at the pelvis and
other joints of the affected lower limb in subjects who were in an early stage
of hip osteoarthritis (OA). DESIGN: Nonrandomized, case-control study. SETTING:
A gait laboratory. PARTICIPANTS: Seventeen patients with OA of the hip (clinical
group) matched with 17 healthy elderly subjects (nonclinical group).
INTERVENTIONS: Video data obtained while subjects walked a 10-meter walkway
twice and stepped across a forceplate. MAIN OUTCOME MEASURES: Four phasic and
temporal gait parameters (walking speed, stance phase relative duration, stride
length, cadence) 10 pelvic (pelvic tilt, obliquity, rotation at push-off maximum
range of motion for all 3) and hip (3 hip angles at push-off, maximum hip
flexion) kinematic parameters, 3 hip moments, and twenty-seven 3-dimensional
peak muscle powers (labeled by joint, peak power, plane) developed in the lower
limb joints during the gait cycle. RESULTS: Subjects in the clinical group were
characterized by a 12.4% slower walking speed. The pelvis was more upwardly
tilted (2.5 times) at push-off in the clinical group than in the nonclinical
group. Obliquity, measured in the frontal plane, revealed that the pelvis
dropped more (2.4 times) on the unsupported limb of the clinical group at
push-off. In the sagittal plane, subjects in the clinical group absorbed less
energy in their second hip peak power for decelerating the thigh extension and
generated less hip pull (third hip peak power) than the nonclinical group by 34%
and 29%, respectively. In the sagittal plane, the clinical group had 57% lower
second knee peak power to straighten the joint shortly after heel strike, and
43% less knee absorption (third peak power) at push-off. During the push-off
phase, the clinical group developed more than twice their third peak knee power
in the frontal plane and 5 times more their third peak knee power in the
transversal plane than the peak knee power of the nonclinical group in an
attempt to control knee adduction and to facilitate body-weight transfer by an
internal rotation. At the end of the swing phase, the fourth peak power in the
sagittal plane showed the absorption power required to decelerate the leg; it
was reduced by 35% in the clinical group, representing a strategy to increase
walking speed by lengthening the stride length. CONCLUSIONS: Even at an early
stage of hip OA, joint degeneration was compensated by an increase in pelvis
motion and muscle power generation or absorption modifications in other lower
limb joints. Copyright 2001 by the American Congress of Rehabilitation Medicine
and the American Academy of Physical Medicine and Rehabilitation
PMID: 11733886 [PubMed - in process]
3: Eur J Biochem 2001 Dec;268(23):6045-57
Synthesis, conformational analysis and biological activity of cyclic analogs of
the octadecaneuropeptide ODN. Design of a potent endozepine antagonist.
Leprince J, Oulyadi H, Vaudry D, Masmoudi O, Gandolfo P, Patte C, Costentin J,
Fauchere JL, Davoust D, Vaudry H, Tonon MC.
Institut Federatif de Recherches Multidisciplinaires sur les Peptides (IFRMP
23), Laboratoire de Neuroendocrinologie Cellulaire et Moleculaire, CNRS,
Universite de Rouen, Mont-Saint-Aignan, France.
The octadecaneuropeptide (ODN; QATVGDVNTDRPGLLDLK) and its C-terminal
octapeptide (OP; RPGLLDLK), which exert anxiogenic activity, have been
previously shown to increase intracellular calcium concentration ([Ca2]i) in
cultured rat astrocytes through activation of a metabotropic receptor positively
coupled to phospholipase C. It has also been found that the [d-Leu5]OP analog
possesses a weak antagonistic activity. The aim of the present study was to
synthesize and characterize cyclic analogs of OP and [d-Leu5]OP. On-resin
homodetic backbone cyclization of OP yielded an analog, cyclo1-8 OP, which was
three times more potent and 1.4-times more efficacious than OP to increase
[Ca2]i in cultured rat astrocytes. Cyclo1-8 OP also mimicked the effect of both
OP and ODN on polyphosphoinositide turnover. Conversely, the cyclo1-8 [d-Leu5]OP
analog was totally devoid of agonistic activity but suppressed the effect of OP
and ODN on [Ca2]i and phosphoinositide metabolism in astrocytes. The structure
of these cyclic analogs has been determined by two-dimensional 1H-NMR and
molecular dynamics. Cyclo1-8 OP exhibited a single conformation characterized by
a gamma turn comprising residues Pro2-Leu4 and a type III beta turn encompassing
residues Leu5-Lys8. Cyclo1-8 [d-Leu5]OP was present as two equimolar conformers
resulting from cis/trans isomerization of the Arg-Pro peptide bond. These
pharmacological and structural data should prove useful for the rational design
of non peptidic ODN analogs.
PMID: 11732998 [PubMed - indexed for MEDLINE]
4: Stat Med 2001 Nov 30;20(22):3335-51
A comparison of several methods to test for the existence of a monotonic
dose-response relationship in clinical and epidemiological studies.
Leuraud K, Benichou J.
University of Rouen Medical School and Rouen University Hospital, CHU de Rouen,
Department of Biostatistics, 1, rue de Germont, 76 031 Rouen Cedex, France.
Biostatistique@chu-rouen.fr
The Mantel-extension chi-square test for overall trend and an asymptotically
equivalent test based on logistic regression are commonly used to test for a
monotonic dose-response relationship between exposure and disease in
epidemiological and clinical studies. However, these tests present two important
disadvantages, as they (i) make the restrictive assumption of a parametric model
of linear form on the logit scale and (ii) impose the a priori choice of scores
to code for the exposure categories. Indeed, the linear assumption, if made
incorrectly, can lead to an invalid conclusion, and the choice of scores lends
arbitrariness to the test results. Some alternative tests have been proposed in
the literature. We have considered several of these tests, namely one based on
isotonic regression, the T-test based on contrasts and a recently published test
based on adjacent contrasts (Dosemeci-Benichou test). The aim of our study was
to compare the statistical properties (type I error and power) of these tests
and of the commonly used Mantel-extension test for overall trend. We generated
cohort and case-control data and considered one- and two-sided versions of the
tests. Moreover, we studied the tests under the null hypothesis of no
relationship between exposure and disease and under various alternative patterns
of monotonic or non-monotonic dose-response relationships. This study confirms
that the commonly used trend tests can lead to erroneous conclusion of a
monotonic dose-response relationship. The test based on isotonic regression does
not represent a favourable alternative, as it tends to be too powerful in case
of non-monotonic dose-response relationship patterns. The tests based on
contrasts seem to possess more favourable properties by combining close to
nominal type I error, high power for monotonic alternatives and low power for
non-monotonic alternatives. Copyright 2001 John Wiley & Sons, Ltd.
PMID: 11746322 [PubMed - indexed for MEDLINE]
5: Brain Res Brain Res Rev 2001 Nov;37(1-3):13-24
Anatomical and biochemical evidence for the synthesis of unconjugated and
sulfated neurosteroids in amphibians.
Mensah-Nyagan AG, Beaujean D, Luu-The V, Pelletier G, Vaudry H.
European Institute for Peptide Research (IFRMP 23), Laboratory of Cellular and
Molecular Neuroendocrinology, Institut National de la Sante et de la Recherche
Medicale (INSERM U-413), Unite Affiliee au Centre National de la Recherche
Scientifique (UA CNRS), University of Rouen, 76821, Mont-Saint-Aignan, France
Various studies have shown that, in mammals, neurons and glial cells are capable
of synthesizing bioactive steroids, or neurosteroids, which regulate the
activity of the central nervous system (CNS). However, although steroid hormones
are involved in the regulation of behavioral and neuroendocrine processes in
amphibians, neurosteroid biosynthesis has never been studied in the CNS of
non-mammalian vertebrates. Reviewed here are several data sets concerning the
production of unconjugated and sulfated neurosteroids in amphibians. These data
were obtained by investigating the immunohistochemical localization and activity
of 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17beta-hydroxysteroid
dehydrogenase (17beta-HSD) and hydroxysteroid sulfotransferase (HST), in the
frog brain. Numerous 3beta-HSD-immunoreactive neurons were detected in the
anterior preoptic area, nucleus of the periventricular organ, posterior
tuberculum, ventral and dorsal hypothalamic nuclei. 17beta-HSD-like
immunoreactivity was found in ependymal gliocytes bordering the lateral
ventricles of the telencephalon. Two populations of HST-immunoreactive neurons
were localized in the anterior preoptic area and the dorsal magnocellular
nucleus of the hypothalamus. High amounts of progesterone (PROG),
17-hydroxyprogesterone (17OH-PROG), testosterone (T) and dehydroepiandrosterone
sulfate (DHEAS) were measured in the frog brain by combining HPLC analysis of
tissue extracts with radioimmunoassay detection. Incubation of telencephalic or
hypothalamic explants with tritiated pregnenolone ([3H]PREG) yielded the
synthesis of various metabolites including PROG, 17OH-PROG, DHEA and T.
Incorporation of [35S]3'-phosphoadenosine 5'-phosphosulfate ([35S]PAPS) and
[3H]PREG or [3H]DHEA into frog brain homogenates led to the formation of
[3H,(35)S]pregnenolone sulfate ([3H,(35)S]PREGS) or [3H,(35)S]DHEAS,
respectively. Altogether, these results demonstrate that the process of
neurosteroid biosynthesis occurs in amphibians as previously seen in mammals.
PMID: 11744071 [PubMed - as supplied by publisher]
6: J Urol 2002 Jan;167(1):236-7
Laparoscopic management of parastomal hernia in transileal urinary diversion.
Dunet F, Pfister C, Denis R, Pascal T, Khalil H, Peillon C.
Department of Digestive Surgery, Rouen University Hospital, Rouen, France.
PMID: 11743315 [PubMed - indexed for MEDLINE]
7: Eur J Heart Fail 2001 Dec;3(6):709-16
Exercise-induced ST-elevation is related to left ventricular dysfunction but not
to myocardial viability in patients with healed myocardial infarction.
Manrique A, Koning R, Hitzel A, Cribier A, Vera P.
GIE de Medecine Nucleaire, Centre Henri Becquerel et CHU de Rouen, 1 rue
d'Amiens, 76038 Cedex, Rouen, France. alain.manrique@rouen.fnclcc.fr
BACKGROUND: Exercise-induced ST-segment elevation was proposed as a marker of
myocardial viability after a recent myocardial infarction. AIMS: The aim of this
study was to evaluate whether exercise-induced ST segment elevation is related
to viability or to left ventricular dysfunction in patients with history of old
Q wave myocardial infarction. METHODS: Fifty patients (43 men, age 5711
years) were studied 3149 months after a Q wave myocardial infarction. They
all underwent stress, reinjection-redistribution, and late redistribution Tl-201
SPECT, completed by equilibrium radionuclide angiography. Viability was defined
by defect reversibility or significant (>60%) persistent Tl-201 uptake in
dyssinergic segments on late redistribution SPECT. Relative post-exercise and
reinjection-redistribution LV volumes were calculated using validated software
(QGS). RESULTS: Twenty-one out of 50 patients (42%, G1) had significant
stress-induced ST-elevation (>1 mm 80 ms after J point in at least 2 ECG leads
with Q wave), and 29/50 (58%, G2) did not. Seventeen out of 50 patients (34%)
demonstrated myocardial viability on late redistribution scan. The diagnostic
accuracy of exercise-induced ST-elevation was only 52% for viability assessment.
Significant LVEF reduction and increased relative LV volumes were observed in G1
compared to G2 (LVEF: 3910% vs. 4911%, P=0.003; post-stress LV volume:
13498 ml vs. 8141 ml, P<0.02; reinjection-redistribution LV volume:
12386 ml vs. 7940 ml; P<0.02). Perfusion defects were similar in G1 and G2
(post-exercise: 3812% vs. 3714%, ns; reinjection-redistribution: 3111%
vs. 3011%, ns; late redistribution: 3010% vs. 2811%, ns). CONCLUSION:
These results suggest that, in patients with history of myocardial infarction,
exercise-induced ST-segment elevation is not related to persistent myocardial
viability but is associated to left ventricular dysfunction.
Publication Types:
Evaluation Studies
PMID: 11738223 [PubMed - indexed for MEDLINE]
8: Am J Respir Crit Care Med 2001 Nov 15;164(10 Pt 1):1933-8
Induction of heme-oxygenase-1 prevents the systemic responses to hemorrhagic
shock.
Tamion F, Richard V, Bonmarchand G, Leroy J, Lebreton JP, Thuillez C.
INSERM E9920, IFRMP and Service de Reanimation Medicale, Rouen University
Hospital, France. fabienne.tamion@chu-rouen.fr
Oxidant-mediated reperfusion injury of the gut is a major contributor of the
systemic inflammatory response in hemorrhagic shock. Recent studies have
suggested that heme-oxygenase-1 (HO-1) represents an endogenous protective
mechanism against oxidant stress. We assessed whether HO-1 induction modulates
the synthesis of tumor necrosis factor-alpha (TNF-alpha) in hemorrhagic shock.
In rats submitted to hemorrhagic shock, pretreatment with hemoglobin (Hb)
increased HO-1 mRNA expression in macrophages. This increased expression was
associated with a decreased expression of TNF-alpha mRNA, as well as decreased
plasma concentrations of TNF-alpha. These effects of Hb were reduced by the HO-1
inhibitor tin-protoporphyrin (Sn-PP 20 micromol/kg), while Sn-PP had no effect
in the absence of Hb. In parallel, Hb pretreatment reduced pulmonary edema,
vascular injury, and increased mesenteric blood flow, and these effects were
reduced by Sn-PP. Thus, induction of HO-1 is protective in hemorrhagic shock,
possibly through its antioxidant properties. Interventions that induce HO-1 may
be beneficial in the treatment of shock states, leading to a reduced systemic
inflammatory response.
PMID: 11734449 [PubMed - indexed for MEDLINE]
9: Gynecol Obstet Fertil 2001 Oct;29(10):723-8
[Breech delivery or cesarean? Must breech delivery be condemned in the case of
breech presentation at term?]
[Article in French]
Marpeau L, Verspyck E.
Clinique gynecologique et obstetricale, CHU Charles-Nicolle, 1, rue de Germont,
76031 Rouen, France.
PMID: 11732439 [PubMed - indexed for MEDLINE]