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M Paillard

Publications and source records attributed to M Paillard.

At least 19 recordsLinked to original sources

Reproducibility of the ventricular synchronization parameters assessed by multiharmonic phase analysis of radionuclide angiography in the normal heart.

Radionuclide angiography (RNA) permits analysis of contractility and conduction abnormalities. We determined the parameters of normal ventricular synchronization, assessed the reproducibility of the technique, and compared first harmonic (1H) and third harmonic (3H) analysis. Forty-four normal subjects (28 men and 16 women) were studied. RNA was performed in left anterior oblique (LAO) and left lateral (LL) projections. The onset (To), mean time (Tm), total contraction time (Tt) for right ventricle (RV) and left ventricle (LV), interventricular time (T(RV-LV) = Tm(LV - Tm(RV)) in LAO, and the apex-to-base time (T(a-b)) in LL were measured on the histograms of the time-activity curve. Reproducibility (R) was tested by studying 26 consecutive patients with two successive RNAs. RV starts contracting 25 ms before LV (To(RV) = 29 +/- 37 ms; To(LV) = 54 +/- 39 ms; mean +/- SD) with a 37 ms longer total contraction time. T(RV-LV) is 3 +/- 16 ms. In LL projection, apex and base contract synchronously: T(a-b) = 2 +/- 16 ms. 3H analysis enlarges all duration parameters (To, Tm and Tt), but does not alter synchronization (deltaT(a-b) and deltaT(RV-LV) between 1H and 3H <1%, p = NS). Reproducibility of the duration (T(tLV) and T(tRv)) and synchronization parameters (T(a-b) and T(RV-LV)) is high (R < or = 2.2%). In conclusion, the simultaneous contraction of right and left ventricles and of apex and base can be quantified by RNA phase analysis with high reproducibility. These results, consistent with published electrophysiological data, provide the basis for further non-invasive investigations of ventricular resynchronization in patients with basal electrical or mechanical asynchrony.

Female↗

[Regulation of the luminal Na+/H+ exchanger NHE3 by intracellular protein trafficking].

The article summarizes some of the recent developments in the understanding of the mechanisms of regulation of the proximal tubule apical membrane Na+/H+ antiporter NHE3. NHE3 antiporter has a major role in HCO3- and NaCl reabsorption in the proximal tubule. NHE3 protein is associated with the regulatory factor NHERF which interacts with ezrin, an actin-binding protein. This multi-protein complex constitutes a link between a membrane protein, NHE3, and actin cytoskeleton. Cytoskeleton organization has a key role to control NHE3 activity under normal conditions. Pharmacological perturbations of actin polymerization interfere with NHE3 activity. Parathyroid hormone-induced NHE3 activity inhibition results first, from a protein kinase A-mediated phosphorylation without protein trafficking, and then from endocytosis involving dynamin. The stimulatory effect of systemic angiotensin II concentrations on NHE3 activity is protein kinase C-dependent and results, at least in part, from exocytic insertion of the protein in luminal membranes. It requires cytoskeleton integrity.

Animals↗

Spin relaxation quenching in semiconductor quantum dots.

We have studied the spin dynamics in self-organized InAs/GaAs quantum dots by time-resolved photoluminescence performed under strictly resonant excitation. At low temperature, we observe strictly no decay of both the linear and the circular luminescence polarization. This demonstrates that the carrier spins are totally frozen on the exciton lifetime scale.

Journal Article↗

[Calcium-sensing receptors: physiology and pathology].

The near constancy of extracellular calcium concentration is required for the numerous physiological functions of extra- and intracellular calcium. This implies that any change in extracellular calcium concentration must be detected in order to allow the appropriate correction by the homeostatic systems. The identification and cloning of a calcium-sensing receptor (CaR), which is expressed in the plasma membrane of parathyroid cells as well as many other cell types, has been a major advance in the understanding of the mechanisms involved in the control of extracellular calcium concentration. In addition, it demonstrated that extracellular calcium concentration itself is the first informative hormone-like messenger in this system. CaR belongs to the C subfamily of seven transmembrane-spanning G protein-coupled receptors. Several inherited disorders in extracellular calcium homeostasis are due to both activating or inactivating mutations in CaR gene, strengthening the essential role of CaR in the control of calcium metabolism.

Calcium↗

Bone status in primary hyperparathyroidism.

Traditional bone involvement, such as osteoitis fibrosa, has become very rare (< 1%) in primary hyperparathyroidism (PHPT); nevertheless, fractures seem more frequent than in controls, with a predilection for fractures of the distal extremity of the radius, pelvis, ribs and vertebrae, and a relative modest incidence of fractures of the upper extremity of the femur. Histo-morphometric studies have stressed a discrepancy between cortical and trabecular bone with an increase of bone remodeling. The cortical width is constantly diminished and the cortical porosity is increased whereas trabecular volume is normal and micro-architecture preserved. Bone mineral density (BMD) allows an early diagnosis of bone disease and takes a growing place in the management of patients. Since the consensus conference in 1991, the measurement of BMD has been incorporated in the surgical decision with a threshold: Z-score < -2. The demineralisation predominates on sites rich in cortical bone (1/3 proximal of the distal radius); the radius, which was the first site evaluated for technical reasons, is also the most discriminating one. Spine demineralisation is met in more severe forms and BMD measurement of the whole body is promising but requires more studies. In the absence of a radical processing, moderate forms remain stable, whereas more severe forms have a tendency to deteriorate. The evaluation of spine and femoral BMD is useful for the follow-up because the bone gain after parathyroidectomy is significant early on at these sites (rich in trabecular bone with high bone turnover), whereas the BMD of radius is relatively stable.

Bone Density↗

Paracellin-1 is critical for magnesium and calcium reabsorption in the human thick ascending limb of Henle.

BACKGROUND: A new protein, named paracellin 1 (PCLN-1), expressed in human thick ascending limb (TAL) tight junctions, possibly plays a critical role in the control of magnesium and calcium reabsorption, since mutations of PCLN-1 are present in the hypomagnesemia hypercalciuria syndrome (HHS). However, no functional experiments have demonstrated that TAL magnesium and calcium reabsorption were actually impaired in patients with HHS. METHODS: Genetic studies were performed in the kindred of two unrelated patients with HHS. Renal magnesium and calcium reabsorption in TAL were analyzed in one homozygous affected patient of each family, one patient with extrarenal hypomagnesemia (ERH), and two control subjects (CSs). RESULTS: We found two yet undescribed mutations of PCLN-1 (Gly 162 Val, Ala 139 Val). In patients with HHS, renal magnesium and calcium reabsorptions were impaired as expected; NaCl renal conservation during NaCl deprivation and NaCl tubular reabsorption in diluting segment were intact. Furosemide infusion in CS markedly increased NaCl, Mg, and Ca urinary excretion rates. In HHS patients, furosemide similarly increased NaCl excretion, but failed to increase Mg and Ca excretion. Acute MgCl(2) infusion in CS and ERH patient provoked a dramatic increase in urinary calcium excretion without change in NaCl excretion. When combined with MgCl(2) infusion, furosemide infusion remained able to induce normal natriuretic response, but was unable to increase urinary magnesium and calcium excretion further. In HHS patients, calciuric response to MgCl(2) infusion was blunted. CONCLUSION: This study is the first to our knowledge to demonstrate that homozygous mutations of PCLN-1 result in a selective defect in paracellular Mg and Ca reabsorption in the TAL, with intact NaCl reabsorption ability at this site. In addition, the study supports a selective physiological effect of basolateral Mg(2+) and Ca(2+) concentration on TAL divalent cation paracellular permeability, that is, PCLN-1 activity.

Adolescent↗

Expression of rat thick limb Na/H exchangers in potassium depletion and chronic metabolic acidosis.

BACKGROUND: Regulation of renal transporter expression has been shown to support adaptation of transporter activities in several chronic situations. Basolateral and apical Na/H exchangers (NHE) in medullary thick ascending limb (MTAL) are involved in NH4+ and HCO3+ absorption, respectively. The NH4+ absorption rate in Henle's loop is increased in chronic metabolic acidosis (CMA) and potassium depletion (KD), which may be secondary to the increased NH4+ concentration in luminal fluid and/or to an increased NH4+ absorptive capacity of MTAL. HCO3- absorptive capacity in Henle's loop is increased in CMA and decreased in metabolic alkalosis, but is unchanged in KD despite the presence of metabolic alkalosis. The present study compared the effects of NH4Cl-induced CMA and KD on the expression of basolateral NHE-1 and the effect of KD on the expression of apical NHE-3 in MTAL. METHODS: NHE-1 and NHE-3 mRNAs and proteins were assessed by a competitive reverse transcription-polymerase chain reaction (RT-PCR) method and semiquantitative immunoblots, respectively, in MTAL-purified suspensions from rats with CMA and KD. RESULTS: NHE-1 protein abundance was similarly increased (approximately 90%) at two and five weeks of KD, while NHE-1 mRNA amount in MTAL cells was increased at two weeks of KD and returned to normal values by five weeks of KD. In contrast, NHE-1 mRNA and protein abundance did not change in CMA. NHE-3 protein abundance remained unchanged in both two and five weeks of KD, while NHE-3 mRNA was unchanged by two weeks of KD and reduced by approximately 50% at five weeks of KD. CONCLUSIONS: The results suggest the following: (1) in KD, where the increased NH4+ concentration of luminal fluid that favors NH4+ absorption is counterbalanced by a decrease in BSC1 expression and activity, the increased NHE-1 expression may support an increased MTAL NH4+ absorptive capacity in CMA, NHE-1 expression is not specifically regulated and remains unchanged, suggesting that the increase in NH4+ concentration in luminal fluid is the main determinant of increased NH4+ absorption in MTAL. (2) In KD, NHE-3 expression did not decrease despite the presence of metabolic alkalosis, in agreement with the unchanged HCO3- absorptive capacity of Henle's loop.

Acidosis↗

NHE3 activity and trafficking depend on the state of actin organization in proximal tubule.

The present study was addressed to define the contribution of cytoskeleton elements in the kidney proximal tubule Na+/H+ exchanger 3 (NHE3) activity under basal conditions. We used luminal membrane vesicles (LMV) isolated from suspensions of rat cortical tubules pretreated with either colchicine (Colch) or cytochalasin D (Cyto D). Colch pretreatment of suspensions (200 microM for 60 min) moderately decreased LMV NHE3 activity. Cyto D pretreatment (1 microM for 60 min) elicited an increase in LMV NHE3 transport activity but did not increase Na-glucose cotransport activity. Cyto D pretreatment of suspensions did not change the apparent affinity of NHE3 for internal H+. In contrast, after Cyto D pretreatment of the suspensions, NHE3 protein abundance was increased in LMV and remained unchanged in cortical cell homogenates. The effect of Cyto D on NHE3 was further assessed with cultures of murine cortical cells. The amount of surface biotinylated NHE3 increased on Cyto D treatment, whereas NHE3 protein abundance was unchanged in cell homogenates. In conclusion, under basal conditions NHE3 activity depends on the state of actin organization possibly involved in trafficking processes between luminal membrane and intracellular compartment.

Actins↗

Localization and functional characterization of Na+/H+ exchanger isoform NHE4 in rat thick ascending limbs.

The Na+/H+ exchanger NHE4 was cloned from a rat stomach cDNA library and shown to be expressed predominantly in the stomach and less dramatically in the kidney. The role and precise localization of NHE4 in the kidney are still unknown. A polyclonal antibody against a unique NHE4 decapeptide was used for immunohistochemistry in rat kidney. Simultaneous use of antibodies to Tamm-Horsfall glycoprotein and aquaporin-2 or -3 permitted identification of thick ascending limbs and collecting ducts, respectively. The results indicate that NHE4 is highly expressed in basolateral membranes of thick ascending limb and distal convoluted tubule, whereas collecting ducts from cortex to inner medulla and proximal tubules showed weaker basolateral NHE4 expression. Western blot analysis of NHE4 in membrane fractions prepared from the inner stripe of the outer medulla revealed the presence of a 95-kDa protein that was enriched in basolateral membrane vesicles isolated from medullary thick ascending limbs. The inhibition curve of H+-activated (22)Na uptake by 5-(N-ethyl-N-isopropyl)amiloride (EIPA) was consistent with the presence, beyond the EIPA high-affinity NHE1 isoform, of an EIPA low-affinity NHE with apparent half-maximal inhibition of 2.5 microM. Kinetic analyses showed that the extracellular Na+ dependence of NHE4 activity followed a simple hyperbolic relationship, with an apparent affinity constant of 12 mM. Intravesicular H+ activated NHE4 by a positive cooperative mechanism. NHE4 had an unusual low affinity for intravesicular H+ with a half-maximal activation value of pK 6.21. We conclude that NHE4, like NHE1, is expressed on the basolateral membrane of multiple nephron segments. Nevertheless, these two proteins exhibited dramatically different affinities for intracellular H+, suggesting that they may play distinct physiological roles in the kidney.

Amiloride↗

[Diurnal consequence of insomnia: impact on quality of life].

Insomnia is not only a disease of sleep, it has also daily consequences: fatigue, irritability, impaired daytime functioning. These complaints are regent reported by the patients, however the objective tests assessing alertness in insomnia are usually not impaired when compared with good sleepers. We wanted to appreciate more accurately the daily consequences of insomnia, in terms of quality of life. 240 severe insomniacs (according to the DSM-IV criterias) and 391 good sleepers received a questionnaire on quality of life items. Depressed and anxious patients were excluded from this group. The questionnaire was built by a multidisciplinary group, based on insomniac's interviews. It was primarily tested in a small sample and then proposed in the entire group. Insomniac's quality of life appeared to be significantly impaired in comparison with good sleepers. They experienced more fatigue and more sleepiness during the daytime. They reported more attention disorders and memory complaints. They seemed to be more irritable and sensitive to the environment. At work they made more mistakes and had more sic leave. They also had poorer relationships with relatives and family than good sleepers.

Adult↗

[Disorders of wakefulness and sleep in blind patients].

The goal of this paper was to summarize three studies focused on sleep/wake disorders in blind subjects. The first study was an epidemiology survey performed in 1073 blind subjects in comparison with non-blind controls. The blind had more episodes of insomnia and free running rhythms. They also took more sleeping pills and complained of more daytime somnolence. The seriousness of the sleep disorders was related to the seriousness of the blindness. In the second study, 78 blind children were compared with seeing children. They had more insomnia and more parasomnias but there was not any more free running. Finally, polysomnography was performed in 26 free running blind subjects in comparison with 26 controls. Total sleep time and sleep efficiency were lower in the blind. Sleep latency was increased and REM sleep was disturbed (longer latency and percentage decreases). There was no difference concerning slow wave sleep. Factorial analysis showed that factors such as being born blind, having ocular prosthesis, being single or having children had no influence on sleep. Working did however have an influence.

Adolescent↗

Prevalence of insomnia in a survey of 12,778 adults in France.

This study was an epidemiological questionnaire survey of a representative sample of the French population that included 12 778 individuals and in which adapted DSM-IV criteria for the definition of insomnia were used. Our goals were not only to assess the prevalence of 'insomnia' using these criteria, but also to compare the results obtained with those of prior studies using different definitions of 'insomnia'. The aim of this study was also to identify where areas of agreement and disagreement existed, as we believe that it is important to emphasize these points because DSM-IV recommendations are supposedly reflected in clinical practice. Seventy-three per cent of the individuals surveyed complained of a nocturnal sleep problem, but only 29% reported at least one sleep problem three times per week for a month, and 19% (2428 subjects) had at least one sleep problem three times per week for a month and complained of daytime consequences (DSM-IV criteria). Only 9% had two or more nocturnal sleep problems with daytime consequences and were classified as 'severe insomniacs'. Our study indicates that if DSM-IV criteria are used, the diagnosis of 'insomnia' is lower than in other epidemiological studies. The DSM criteria have an advantage in that they emphasize the daytime consequences of nocturnal sleep disturbances, which seem to be responsible for the most important socio-economic costs of the problem.

Adolescent↗

Biventricular pacing in severe heart failure patients reverses electromechanical dyssynchronization from apex to base.

Biventricular (BV) pacing is an emerging treatment for patients with severe dilated cardiomyopathy and ventricular asynchrony. Radionuclide angioscintigraphy has shown that BV can reduce activation delays between left (LV) and right ventricles (RV), but alterations of electromechanical asynchrony between the LV base and apex have not been previously described. Radionuclide angioscintigraphy with Tc99m red cell labeling was performed in 21 patients, 64 +/- 17 years of age, in NYHA functional Class III or IV, and with a mean QRS duration of 180 +/- 15 ms. Right (RVEF) and LV ejection fraction (LVEF), and the synchronization between LV apex and base (Tab) in the left lateral view, were measured by a phase analysis program (1) at baseline, (2) on day 8 after BV pacemaker implantation (D8), and (3) at 12-month follow-up in BV (M12). BV pacing reversed Tab from 42 +/- 47 ms at baseline to -57 +/- 75** on D8, and -37 +/- 76** on M12. LVEF increased from 17.8 +/- 6.3% to 19.9 +/- 8.3 on D8, and 24.2 +/- 10.8* on M12, and RVEF increased from 27.6 +/- 16% to 29.9 +/- 16 on D8 and 34.1 +/- 12.1* on M12 (*P < 0.05, **P < 0.001). A close correlation was found between early LV apex-to-base resynchronization induced by BV and late increase in LVEF (r = 0.59**). In parallel with its known interventricular resynchronization effect, BV pacing reverses the apex-to-base ventricular activation sequence, causing early contraction of the LV base followed by the apex. These changes persisted up to 12 months along with an improvement in LV systolic function.

Cardiac Output↗

[Primary hyperparathyroidism].

Primary hyperparathyroidism is the third most frequent endocrine disorder. The condition required for diagnosis is inappropriately elevated secretion of parathyroid hormone (PTH) with respect to calcemia. Most often, the disease is due to a parathyroid adenoma, i.e. a monoclonal benign parathyroid tumor, less often to a parathyroid hyperplasia. The main tumorogenic mechanisms currently proposed are a DNA rearrangement in the PTH locus (transposition of the PTH promoter upstream to Cyclin D1/PRAD 1 gene) and a mutation of the gene responsible for multiple endocrine neoplasia type I. The clinical presentation has strikingly evolved towards a milder, asymptomatic form, frequently diagnosed on systematic screenings. Though the mechanism of hypercalcemia is better understood, several hypothesis are still being considered about the regulation of tumoral PTH secretion: the role of the expression of calcium-receptor in parathyroid gland cells, vitamin D receptor and estrogen receptor polymorphisms, etc. Surgery is still advised for symptomatic forms of the disease, either because of a bone involvement, or because of an evolutive nephrolithiasis. In the near future, the new calcium-receptor agonists could be a relevant therapeutic approach.

Humans↗

Polarized expression of different monocarboxylate transporters in rat medullary thick limbs of Henle.

Extracellular lactic acid is a major fuel for the mammalian medullary thick ascending limb (MTAL), whereas under anoxic conditions, this nephron segment generates a large amount of lactic acid, which needs to be excreted. We therefore evaluated, at both the functional and molecular levels, the possible presence of monocarboxylate transporters in basolateral (BLMVs) and luminal (LMVs) membrane vesicles isolated from rat MTALs. Imposing an inward H(+) gradient induced the transient uphill accumulation of L-[(14)C]lactate in both types of vesicles. However, whereas the pH gradient-stimulated uptake of L-[(14)C]lactate in BLMVs was inhibited by anion transport blockers such as alpha-cyano-4-hydroxycinnamate, 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS), and furosemide, it was unaffected by these agents in LMVs, indicating the presence of a L-lactate/H(+) cotransporter in BLMVs, but not in LMVs. Under non-pH gradient conditions, however, the uptake of L-[(14)C]lactate in LMVs was transstimulated 100% by L-lactate, but by only 30% by D-lactate. Furthermore, this L-lactate self-exchange was markedly inhibited by alpha-cyano-4-hydroxycinnamate and DIDS and almost completely by 1 mM furosemide, findings consistent with the existence of a stereospecific carrier-mediated lactate transport system in LMVs. Using immunofluorescence confocal microscopy and immunoblotting, the monocarboxylate transporter (MCT)-2 isoform was shown to be specifically expressed on the basolateral domain of the rat MTAL, whereas the MCT1 isoform could not be detected in this nephron segment. This study thus demonstrates the presence of different monocarboxylate transporters in rat MTALs; the basolateral H(+)/L-lactate cotransporter (MCT2) and the luminal H(+)-independent organic anion exchanger are adapted to play distinct roles in the transport of monocarboxylates in MTALs.

Animals↗

The direct costs of insomnia in France.

Several reports indicate that use of hypnotics is significantly higher in France relative to other European countries, but few reports exist concerning the cost of this high consumption of psychotropic medications. The purpose of the present study was to estimate the direct costs that may be attributed to insomnia in France. Data were derived from previously published surveys in this field. It includes the cost of sleep medications and of substances used to promote sleep, outpatient visits to physicians or to other health professionals and sleep recordings and treatment by sleep specialists. The final estimate of the total direct cost of insomnia in France in 1995 was FF 10,232,992,500 ($2,067,271,100). Public authorities have to understand that an increase in the direct costs of insomnia may be balanced by the reduction of the daytime consequences of insomnia and then by the reduction of the indirect costs of insomnia.

Adolescent↗