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Biomedical subjects

P Mollard

Publications and source records attributed to P Mollard.

At least 37 records · Page 2Linked to original sources

Continent cystostomy (Mitrofanoff's procedure) for neurogenic bladder in children and adolescent (56 cases: long-term results).

Between 1978 and 1991 we made a continent cystostomy according to Mitrofanoff's technique in 56 patients - children or adolescents - with a neurogenic bladder. We study the complications and the long-term results (follow-up ranging from 3 to 17 years - average 10 years). One patient died from a urological complication, another one died 2 years after from a neurological complication. Two patients were lost to follow-up after 3 years. Among the other patients 36 i.e. 64.3% have had urological complications. Analysis of these complications and their treatment demonstrates that most could now be avoided. At the present time the continent cystostomy with an appendicular or ureteral conduit is the safest and most comfortable way to treat the incontinence of wheel-chair bound patients who cannot or do not wish to use transurethral catheterisation.

Adolescent↗

Female epispadias.

PURPOSE: We assessed the incidence, anatomical features and treatment of female epispadias. MATERIALS AND METHODS: We studied 10 patients followed from 1 to 18 years. Four were operated on in 2 stages: first, cervicoplasty with original technique, and second, reconstruction of genitalia and distal urethra. Two had only a cervicoplasty. The last 4 patients were operated on in 1 stage according to Hendren's technique but with a simplified cervicoplasty. RESULTS: Eight of 10 patients are totally continent, 1 has some small nocturnal leakage, and 1 is incontinent but the interval of dryness is increasing and is longer than 1 hour. Concerning external genitalia, the result is good but not perfect. CONCLUSIONS: Female epispadias is most often complete with total incontinence. The aim of treatment is to reconstruct the anatomy in 1 stage. Treatment is easier and the results are better than in cases of female exstrophy or male incontinent epispadias.

Adolescent↗

[Urethral lengthening (the Kropp technic) in neurologic urinary incontinence in children and adolescents. Results of a series of 22 cases].

In 1986 Kropp et Angwafo described a technique of urethral lengthening for the treatment of urinary incontinence in children with neurogenic bladders. We have used a modified version of this procedure in 22 girls between 1986 and 1990. Here we report its mid and long term effects on continence. The problems we have encountered in these patients are discussed.

Adolescent↗

Spontaneous and gonadotropin-releasing hormone-stimulated cytosolic calcium rises in individual goldfish gonadotrophs.

The cytosolic free calcium concentration, [Ca2+]i, was monitored in single isolated goldfish gonadotrophs with the fluorescent probe Indo-1. It was found that goldfish gonadotrophs exhibit both spontaneous and secretagogue-induced [Ca2+]i rises. Spontaneous [Ca2+]i transients showed striking kinetic features and a sensitivity to external Ca2+ suggesting that they were the consequence of transient Ca2+ entries. Two kinetically distinct patterns of [Ca2+]i rises were generated in response to the two native forms of gonadotropin-releasing hormone (GnRH), salmon GnRH (sGnRH) and chicken GnRH-II (cGnRH-II). In a part of the gonadotrophs, GnRHs triggered a plateau [Ca2+]i rise whereas in other responsive cells they induced a series of [Ca2+]i bursts, each consisting of grouped [Ca2+]i transients. Both plateau and burst [Ca2+]i response patterns were due to Ca2+ entry through plasma membrane Ca2+ channels, inasmuch as they were suppressed with external Ca2+ removal. No contribution of Ca2+ release from thapsigargin-sensitive stores was observed in either response pattern. While in mammalian gonadotrophs GnRH rises [Ca2+] by mostly acting on internal Ca2+ sequestering stores, our results show that GnRH-stimulated goldfish gonadotrophs rapidly increase Ca2+ entry to enhance their [Ca2+]i levels.

Animals↗

Artificial urinary sphincter implantation for neurogenic bladder: a multi-institutional study in 107 children.

OBJECTIVES: To evaluate the outcome of implantation of the AMS 800 artificial urinary sphincter in children with neurogenic bladder. PATIENTS AND METHODS: The records of 107 children (74 boys and 33 girls) treated for neurogenic urinary incontinence by implantation of the AMS 800 artificial sphincter between 1983 and 1993 were reviewed retrospectively. The underlying cause of incontinence in 92 patients was spina bifida, the mean age at implantation was 13.7 years and 30 patients had undergone previous bladder neck surgery. Implantation was carried out in combination with another surgical procedure in 24.3% of patients. The mean follow-up was 61 months (minimum 12). RESULTS: The mean operational life of the sphincter was 56 months. No deaths occurred but removal of the artificial sphincter was necessary in 20 patients (19%). Surgical revision was not required in 44 patients (41%) but at least one revision was performed in 63 and more than one in 42. There were 21 mechanical failures, 40 surgical complications and 39 cases involving changes in the dynamics of bladder function. Of the 87 children (81%) in whom the device is still in place, 72 are completely continent (83%), 10 are slightly wet, and five are incontinent. The overall success rate was 77%. CONCLUSIONS: The results emphasize that for successful implantation of an artificial urinary sphincter in children, the pre-operative bladder capacity must be sufficient and previous surgery should not have been performed on the bladder neck, the site of choice for implantation in children. Sphincterotomy is not always necessary in paediatric patients. Children and parents should be informed of the high complication rate and the need for long-term follow-up.

Adolescent↗

Direct observation of serotonin 5-HT3 receptor-induced increases in calcium levels in individual brain nerve terminals.

Confocal microscopy was used to assess internal calcium level changes in response to presynaptic receptor activation in individual, isolated nerve terminals (synaptosomes) from rat corpus striatum, focusing, in particular, on the serotonin 5-HT3 receptor, a ligand-gated ion channel. The 5-HT3 receptor agonist-induced calcium level changes in individual synaptosomes were compared with responses evoked by K+ depolarization. Using the fluorescent dye fluo-3 to measure relative changes in internal free Ca2+ concentration ([Ca2+]i), K+-induced depolarization resulted in variable but rapid increases in apparent [Ca2+]i among the individual terminals, with some synaptosomes displaying large transient [Ca2+]i peaks of varying size (two- to 12-fold over basal levels) followed by an apparent plateau phase, whereas others displayed only a rise to a sustained plateau level of [Ca2+]i (two- to 2.5-fold over basal levels). Agonist activation of 5-HT3 receptors induced slow increases in [Ca2+]i (rise time, 15-20 s) in a subset (approximately 5%) of corpus striatal synaptosomes, with the increases (averaging 2.2-fold over basal) being dependent on Ca2+ entry and inhibited by millimolar external Mg2+. We conclude that significant increases in brain nerve terminal Ca2+, rivaling that found in response to excitation by depolarization but having distinct kinetic properties, can therefore result from the activation of presynaptic ligand-gated ion channels.

Animals↗

[Current treatment of hypospadias].

The aim of this work was to discuss general ideas concerning the factors which should be taken into account for the treatment of hypospadia including: anatomy, preoperative work-up, analysis of the anatomic type, patient status, search for an underlying more complex malformation. Precise indications for per and post-operative care should provide good results. Two major ideas predomination in these recommendations: operate early (at about 2 years) in a single procedure for both anatomic and psychological reasons. This latter point is particularly important. Operative technique is illustrated and described together with complications and their management.

Humans↗

Activation of nicotinic receptors triggers exocytosis from bovine chromaffin cells in the absence of membrane depolarization.

The traditional function of neurotransmitter-gated ion channels is to induce rapid changes in electrical activity. Channels that are Ca(2+)-permeable, such as N-methyl-D-aspartate receptors at depolarized membrane potentials, can have a broader repertoire of consequences, including changes in synaptic efficacy, developmental plasticity, and excitotoxicity. Neuronal nicotinic receptors for acetylcholine (nAChRs) are usually less Ca(2+)-permeable than N-methyl-D-aspartate receptors but have a significant Ca2+ permeability, which is greater at negative potentials. Here we report that in neuroendocrine cells, activation of nAChRs can trigger exocytosis at hyperpolarized potentials. We used whole-cell patch-clamp recordings to record currents and the capacitance detection technique to monitor exocytosis in isolated bovine chromaffin cells. Stimulation of nAChRs at hyperpolarized potentials (-60 or -90 mV) evokes a large current and a maximal capacitance increase corresponding to the fusion of approximately 200 large dense-core vesicles. The amount of exocytosis is controlled both by the Ca2+ influx through nAChRs and by a contribution from thapsigargin-sensitive Ca2+ sequestering stores. This is a form of neurotransmitter action in which activation of nAChRs triggers secretion through an additional coupling pathway that coexists with classical voltage-dependent Ca2+ entry.

Adrenal Medulla↗

Modulation of a volume-regulated chloride current by F-actin.

We have examined whether F-actin integrity is involved in activation of a volume-regulated Cl- current (VRChlC) in B-lymphocytes. VRChlC activation was initiated in response to establishing a whole cell recording in the presence of a hyposmotic gradient. Parallel confocal microscopy experiments using Rhodamine-Phalloidin (R-P) as a specific marker of F-actin showed that the submembrane actin ring is reversibly disrupted in response to an hyposmotic gradient. Disruptions of cortical F-actin integrity by 50 microM cytochalasin B (CB) does not trigger activation of VRChlC under isosmotic conditions or potentiate the rate of activation when the osmolarity of the extracellular solution was decreased by 75%. However, incubation with CB increased the rate of VRChlC activation in response to a 90% hyposmotic gradient. Phalloidin, a stabilizer of F-actin, decreases the rate of VRChlC activation in response to a 90% gradient, but has no effect in response to a 75% gradient. These observations suggest that disassembly of cortical F-actin is not critical for VRChlC activation in B-lymphocytes. The integrity of cortical F-actin, however, can exert a modulatory effect on the rate of VRChlC activation in the presence of a hyposmotic gradient.

Actins↗

[Urodynamic exploration in functional micturition disorders in children].

Urodynamic investigation in paediatric patients is presented. The practical aspects and usefulness of each method are discussed in the cases of functional micturition disorders based upon the most significant results from the literature and the author's experience. Urodynamic investigation in children provides a pathophysiological explanation of bladder-sphincter dysfunction and guidelines for appropriate treatment.

Anal Canal↗

Tumor-related selection of calcium signals in vasopressin-stimulated human adenomatous corticotrophs.

The action of arginine vasopressin (AVP) on cytosolic free calcium concentration ([Ca2+]i) was studied at the single-cell level in corticotrophs cultured from pituitary adenoma fragments removed from eight patients with Cushing's disease. AVP evoked distinct [Ca2+]i responses with regard to the tumor origin. In cells from two tumors, AVP consistently evoked a series of characteristic elevations of [Ca2+]i (transient pattern) that depended on Ca2+ entry. In cells from the other tumors, AVP triggered different patterns of [Ca2+]i rise, which consisted of low-amplitude slow monophasic increases at low AVP concentration and a high-amplitude spike increase followed by a sustained plateau (spike-plateau pattern) at higher concentration of AVP. Slow monophasic increases and the spike of spike-plateau responses were due to calcium release from internal stores, whereas the plateau was a consequence of calcium entry. These two patterns (transient vs. spike-plateau) resemble those observed in subpopulations of corticotrophs from healthy rat pituitary glands (Corcuff et al., J. Biol. Chem. 268: 22313-22321, 1993), suggesting that tumorigenesis can lead in pituitary tissues to a selection rather than alteration of AVP [Ca2+]i signals.

Adenoma↗

Cytosolic Ca2+ of excitable pituitary cells at resting potentials is controlled by steady state Ca2+ currents sensitive to dihydropyridines.

Different elements of voltage-gated Ca2+ influx and their role for cytosolic-free Ca2+, [Ca2+]i, were studied in cells of the pituitary line GH3B6. Single cell monitoring of [Ca2+]i with the fluorescent probe indo-1, as well as fast on-line ratio [Ca2+]i imaging with fura-2, were combined with electrophysiological recordings using the perforated patch configuration of the patch clamp technique. [Ca2+]i signals are generated by Ca2+ influx both during action potentials and in between. Steady state Ca2+ influx at resting potentials (-60 to -40 mV) was voltage-gated and sensitive to the dihydropyridine antagonist PN 200-110. Ca2+ influx could be demonstrated in physiological conditions as inward Ca2+ currents of maximally 10 pA, which were triggered when stepping up the holding voltage beyond a narrow threshold around -50 mV. Inward currents were well correlated with [Ca2+]i elevations (R = -0.8; p < 0.001). It is concluded that dihydropyridine-sensitive, low threshold voltage-gated steady state Ca2+ currents, which may be tonically activated at resting potentials, provide for [Ca2+]i signaling in excitable endocrine cells in a mode that parallels the modulation of Ca2+ influx during action potentials.

Animals↗

Effects of two neuronal antidiuretic molecules, neuroparsin and 5-hydroxytryptamine, on cytosolic free calcium monitored with indo-1 in epithelial and muscular cells of the African locust rectum.

Using the probe indo-1 in a microspectrofluorimetric study, it was demonstrated that the locust antidiuretic neurohormone, neuroparsin, enhanced cytosolic free Ca2+ concentrations, measured as percentages of the ratio F405/F480 (R), in epithelial cells of the African locust rectum. 5-hydroxytryptamine, whose antidiuretic effect was previously established, enhanced R in longitudinal muscular cells, and was able to increase R slightly in epithelial cells. The possibility of reciprocal Ca2+ movements between muscular and epithelial cells is discussed. Both of the neuronal molecules, which act via distinct transduction pathways (phosphoinositide turnover for neuroparsin, and Ca(2+)-dependent adenylate cyclase for 5-hydroxytryptamine), stimulated an increase in R by causing Ca2+ entry through dihydropyridine-sensitive Ca2+ channels. Cyclic nucleotides (cAMP and cGMP) lowered R in epithelial cells, the cGMP effect being interpreted as a feedback control on phosphoinositide turnover and resulting in the ability to re-establish cAMP production to levels incompatible with high PLC activity. In longitudinal muscular cells, the increase in R due to cAMP suggests the involvement of 5-hydroxytryptamine in stimulation of adenylate cyclase activity. Furthermore, results enabled the localization in epithelial cells of the transduction pathways mediating the actions of another antidiuretic factor extracted from the glandular lobes of the locust corpora cardiaca.

Animals↗

Hypospadias: the release of chordee without dividing the urethral plate and onlay island flap (92 cases)

Standard teaching states that the correction of fibrous chordee requires division of the urethral plate. Subsequently, it is necessary to reconstruct the urethra using tubular urethroplasty, which carries a significant incidence of complications, for example stenosis. In fact, we have demonstrated that it is possible to release severe chordee associated with hypospadias simply by dissecting the urethral plate of the corpora rather than dividing it. Between 1989 and 1993 we operated on 101 patients with hypospadias with fibrous chordee. The release of chordee was achieved without dividing the plate in 92 patients (91%), including all 71 cases of penile hypospadias, 11 perineal hypospadias and 10 reoperations. A total of 92 urethroplasties was performed with an onlay flap and 19 complications occurred in 15 patients.

Child↗

Urinary continence after reconstruction of classical bladder exstrophy (73 cases)

OBJECTIVE: To evaluate urinary continence in children after reconstruction of classical bladder exstrophy. PATIENTS AND METHODS: Seventy-three children were treated between 1966 and 1990 at Debrousse Hospital in Lyon, France. Reconstruction involved a three-stage repair including bladder closure (with posterior iliac osteotomy), bladder neck reconstruction and penile reconstruction. RESULTS: Of 73 children with bladder exstrophy, seven underwent an initial urinary diversion and 66 a successful bladder closure at birth combined with posterior iliac osteotomy, 55 of whom underwent a bladder neck reconstruction and anti-reflux procedures. The Young-Dees procedure was performed in four cases, combined with the Jeff's technique in two cases and the Mollard technique in 49. Fifty-four of 55 (22 girls and 32 boys) were followed up for between 1 and 17 years. Results were classified as excellent (37 cases), good (11 cases) or failed (six cases), following assessment of continence, voiding capabilities, residual urine volume, urinary tract infection and urinary tract dilatation. Of these patients 69% had normal continence with transurethral voiding (girls, 77%; boys, 63%). Persistent incontinence after bladder neck reconstruction was related to insufficient outlet resistance, an abnormal bladder or a combination of the two. Repeated bladder neck reconstruction (seven patients), bladder augmentation (five patients), bladder neck suspension (one patient) and bladder neck reconstruction combined with augmentation (five patients) were performed. These operations were coupled with a Mitrofanoff procedure if further complications occurred. CONCLUSION: The outcome of bladder neck reconstruction was unpredictable. Achievement of a balance between intravesical pressure and outlet resistance was difficult and often required secondary endourethral procedures. Persistent incontinence after bladder neck reconstruction was related to insufficient outlet resistance, an abnormal bladder or a combination of the two. Repeated bladder neck reconstruction, bladder augmentation, bladder neck suspension and reconstruction combined with augmentation were performed. These operations were coupled with a Mitrofanoff procedure, which offered catheterization as a safe alternative if further complications occurred.

Bladder Exstrophy↗

Prolactin and growth hormone release and calcium influx are stimulated by galanin within a 'window' range of concentrations in pituitary GH3 B6 cells.

Galanin is widely distributed throughout the rat neural and endocrine system with the highest concentration in the anterior pituitary. The effects of galanin were investigated in rat tumor pituitary cells (GH3/B6). A single stimulation with galanin caused prolactin (PRL) and growth hormone (GH) release within a narrow range of concentrations (10(-11)-10(-9) M). However, secretory responses were not consistently observed upon subsequent galanin stimulation. Galanin triggered a rise in cytosolic Ca2+ (burst in [Ca2+]i transients) with a similar responsiveness. By contrast, no change in PRL mRNA was detectable in response to the peptide. These data suggest that galanin which binds to high-affinity receptors in anterior pituitary cells can exert subtle modulations of pituitary cell functions.

Animals↗

Multiple cytosolic calcium signals and membrane electrical events evoked in single arginine vasopressin-stimulated corticotrophs.

The action of arginine vasopressin (AVP) on cytosolic free Ca2+ concentration ([Ca2+]i) was investigated in single rat pituitary corticotrophs using indo-1 microfluorimetry, in part in combination with the monitoring of membrane electrical events with the perforated patch-clamp technique. In corticotrophs showing the series of short-lived [Ca2+]i rises (transient pattern) in response to corticotropin-releasing factor, 100 nM AVP evoked either the transient pattern or a [Ca2+]i spike followed by a sustained plateau (spike/plateau pattern). Not all corticotrophs responded to changes in AVP concentration in the same manner. Some cells exhibited a concentration-dependent increase in [Ca2+]i transient activity, whereas others showing the spike/plateau at high AVP concentrations responded to low agonist concentrations by two [Ca2+]i responses: a slow rising step or two to three sinusoidal-like oscillations. Combined [Ca2+]i and patch-clamp recordings as well as manipulation of extracellular Ca2+ showed that both transient pattern and the plateau of spike/plateau response depended on Ca2+ entry mainly through voltage-gated, dihydropyridine-sensitive Ca2+ channels. By contrast, step, oscillations, and spike were due to Ca2+ release from internal stores. These Ca(2+)-mobilizing responses caused the activation of Ca(2+)-activated, apamin-sensitive K+ channels, which led to a membrane hyperpolarization. These results reveal cell-specific [Ca2+]i signals and associated electrical events in individual AVP-stimulated corticotrophs.

Animals↗

Characterization of Ca2+ signals generated by extracellular nucleotides in supporting cells of the organ of Corti.

ATP has been demonstrated to act as a co-transmitter or neuromodulator in various physiological processes. There is recent evidence that ATP receptors, characterized as P2 purinergic receptors, are expressed in the sensory hair cells of the auditory organ. The aim of the present study was to know whether other cell types of the organ of Corti, the supporting cells, were also sensitive to external ATP. In both types of supporting cells considered in this study, Deiters' cells (DCs) and Hensen's cells (HEs), extracellular ATP at sub-micromolar concentrations evoked a transient increase in [Ca2+]i as monitored with fluorescence microscopy using the calcium probe Indo-1. An apparent Kd of 0.5 and 0.9 microM was determined for DCs and HEs, respectively. Furthermore, we demonstrated that ATP stimulated Ca2+ release from internal stores in DCs, but not in HEs. Dynamic calcium imaging by confocal laser scanning microscopy of ATP induced Ca2+ mobilization demonstrated a calcium wave propagation in the cell body of DCs which originated in the phalangeal processes, suggesting a functional organization of Ca2+ sequestering stores in DCs.

Adenosine Triphosphate↗