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Biomedical subjects

A Raes

Publications and source records attributed to A Raes.

At least 19 recordsLinked to original sources
PubMed2000

Pelvic-floor therapy and toilet training in young children with dysfunctional voiding and obstipation.

OBJECTIVE: To analyse experience in treating young children (4-5 years old) with urodynamically confirmed voiding dysfunction, using a noninvasive training programme. PATIENTS AND METHODS: Between January 1996 and October 1997, 20 children (all < 5 years old, mean age 4.45 years, 18 girls and two boys, mean ages 4.44 and 4.5 years, respectively) with voiding dysfunction were treated. Three children showed filling phase dysfunction alone (bladder instability), six emptying phase dysfunction alone (dysfunctional voiding) and 11 showed both filling and emptying phase dysfunction. Sixteen children had incontinence problems (three diurnal, two nocturnal and 11 diurnal and nocturnal). Eight children had a history of recurrent urinary tract infections and 12 girls had vaginal irritation. Four children were referred for perineal pain caused by spasms of the pelvic floor. Eight children had encopresis based on chronic obstipation. Therapy consisted of keeping a voiding and drinking chart, instructions on proper toilet posture, daily rules for application at home, and if possible relaxation biofeedback of the pelvic-floor muscles. Therapy was considered successful if incontinence and other urological symptoms resolved. The treatment of encopresis is also discussed. RESULTS: Of the 20 children, 13 had a good result; they all became dry during the day and night, and encopresis resolved. Six children had moderate success; in one, nocturnal incontinence persisted, and in two diurnal and nocturnal incontinence continued. In two children encopresis persisted and in one the faecal incontinence ameliorated. In one child the therapy was prematurely interrupted because of lack of motivation. CONCLUSION: This experience suggests that a noninvasive training programme is applicable in very young children with symptoms of dysfunctional elimination of urine and faeces.

Biofeedback, Psychology↗
PubMed1999

Uraemic guanidino compounds inhibit gamma-aminobutyric acid-evoked whole cell currents in mouse spinal cord neurones.

Guanidine, creatinine (CTN), methylguanidine (MG) and guanidinosuccinic acid (GSA) are four endogenous guanidino compounds with proven neuroexcitatory actions, and putative pathophysiological significance as uraemic toxins. The effects of these uraemic guanidino compounds, were studied on whole-cell current evoked by gamma-amino butyric acid (GABA) on mouse spinal cord neurones in vitro. CTN, MG and GSA concentration dependently blocked GABA-evoked current with calculated IC50 values (+/-SE) of 9.6 +/- 0.9, 9.7 +/- 1.5 and 5.1 +/- 0.4 mM, respectively. CTN, MG and GSA were shown to block inward and outward currents to the same extent, demonstrating voltage independent block of GABA-evoked current by these compounds. Guanidine, however, evoked inward whole-cell currents, which were almost completely blocked by strychnine, indicating that the guanidine-evoked current might have been due to glycine receptor activation.

Animals↗
PubMed1999

Anomalies of the external urethral meatus in girls with non-neurogenic bladder sphincter dysfunction.

OBJECTIVE: To investigate in a prospective study the clinical and urodynamic characteristics associated with the correlation previously reported between non-neuropathic bladder sphincter dysfunction and minimal meatal deformities in girls. PATIENTS AND METHODS: From January 1995 to June 1996 all girls referred for urodynamics to investigate non-neuropathic bladder sphincter dysfunction were examined for meatal anomalies. Two types of meatal anomalies were recognized, i.e. hypospadias, in which the urethral meatus is displaced dorsally and meatal web or covered hypospadias, in which there is a mucosal web on the dorsal side of the urethral meatus that deflects the urinary stream anteriorly. The girls presenting with minimal meatal deformities were compared with those presenting a normal meatal configuration for their history and video-urodynamic features. RESULTS: During the study, 288 girls were referred for video-urodynamics; 88 presented with meatal anomalies (24 hypospadias and 64 covered hypospadias) and comprised the study group; all other girls were considered as the control group. Incontinence during the day was more frequent in the study group (56%) than in the control group (34%) (P=0.003). Nocturnal enuresis was more frequent in the control group (87%) than in the study group (68%, P=0.006). Urge was more frequent in the study group (80%) than in the control group (65%, P=0.02), as was anterior deflection of the urinary stream (voiding over the toilet rim), in 48% and 4.5%, respectively (P<0.001). On video-urodynamics, dysfunctional voiding (detrusor sphincter dyscoordination during voiding) was more frequent in the study group (59%) than in the control group (38%, P=0.009), and vaginal voiding was more frequent in the study group (40%) than in the control group (11.5%, P<0.001). CONCLUSION: Girls presenting with meatal anomalies have more severe dysfunction, as estimated by urodynamics. Although the natural history of these anomalies and the incidence in the normal population is not known, it is thought that there is an aetiological correlation between the functional voiding disorders and the meatal anomaly. Surgical treatment to correct the anomalies is proposed.

Female↗
PubMed1999

Effects of competitive NMDA receptor antagonists on excitatory amino acid-evoked currents in mouse spinal cord neurones.

The effects of CGP 37849 [DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoate] and its ethylester CGP 39551 on whole-cell currents evoked by the endogenous excitatory amino acids, L-glutamate and L-aspartate, were studied in cultured mouse spinal cord neurones. Although CGP 37849 was the more potent compound, both antagonists inhibited 20 microM L-aspartate or 2 microM L-glutamate currents concentration-dependently and reversibly. We calculated IC50 values of 370 +/- 180 nM for CGP 37849 and 2200 +/- 140 nM for CGP 39551 (inhibition of L-aspartate current), and 210 +/- 25 nM for CGP 37849 and 6000 +/- 4700 nM for CGP 39551 (inhibition of L-glutamate current). Both CGP 37849 and CGP 39551 selectively blocked N-methyl-D-aspartate (NMDA)-evoked inward current. Current evoked by 5 microM kainate or 5 microM alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) was unaffected by 10 microM CGP 39551. Current evoked by NMDA was concentration-dependently blocked by CGP 39551 with an IC50 of 2100 +/- 220 nM. After application of 10 microM CGP 37849, 17 +/- 6% of the current evoked by 5 microM L-glutamate remained. This residual current was due to non-NMDA receptor activation since application of 25 microM 2-amino-5-phosphonovalerate (APV) together with CGP 37849 did not significantly alter the residual current, whereas application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) with CGP 37849 did significantly inhibit this current. Clamping cells at potentials ranging from -80 to +60 mV showed a linear potential--current relationship for the 20 microM L-aspartate-evoked current with reversal potential around 0 mV. The proportion of the L-aspartate current antagonized by CGP 37849 or CGP 39551 appeared to be independent of clamping potential. The concentration--current relationship of L-aspartate in the absence of the antagonists showed an EC50 of 49 +/- 14 microM. Upon application of 1 microM CGP 37849 and 10 microM CGP 39551, the L-aspartate concentration--current curve shifted to higher concentrations, and resulted in a 5- and 13-fold increase in the EC50 of L-aspartate, respectively, whereas Imax was not changed by application of the antagonists. Thus, the potent NMDA antagonists CGP 37849 and CGP 39551 were shown to inhibit excitatory amino acid responses specifically by competitive binding to the neurotransmitter recognition site of the NMDA receptor. Selective, competitive antagonism of L-glutamate- and L-aspartate-evoked NMDA receptor responses probably underlies the effects of CGP 37849 and CGP 39551 such as their anticonvulsant, neuroprotectant and antidepressant actions.

2-Amino-5-phosphonovalerate↗
PubMed1998

A K+ channel splice variant common in human heart lacks a C-terminal domain required for expression of rapidly activating delayed rectifier current.

We have cloned HERG USO, a C-terminal splice variant of the human ether-à-go-go-related gene (HERG), the gene encoding the rapid component of the delayed rectifier (IKr), from human heart, and we find that its mRNA is approximately 2-fold more abundant than that for HERG1 (the originally described cDNA). After transfection of HERG USO in Ltk- cells, no current was observed. However, coexpression of HERG USO with HERG1 modified IKr by decreasing its amplitude, accelerating its activation, and shifting the voltage dependence of activation 8.8 mV negative. As with HERG USO, HERGDeltaC (a HERG1 construct lacking the C-terminal 462 amino acids) also produced no current in transfected cells. However, IKr was rescued by ligation of 104 amino acids from the C terminus of HERG1 to the C terminus of HERGDeltaC, indicating that the C terminus of HERG1 includes a domain (</=104 amino acids) that is critical for faithful recapitulation of IKr. The lack of this C-terminal domain not only explains the finding that HERG USO does not generate IKr but also indicates a similar mechanism for hitherto-uncharacterized long QT syndrome HERG mutations that disrupt the splice site or the C-terminal. We suggest that the amplitude and gating of cardiac IKr depends on expression of both HERG1 and HERG USO.

Alternative Splicing↗
PubMed1998

Use-dependent block of Ih in mouse dorsal root ganglion neurons by sinus node inhibitors.

1. The sinus node inhibitors UL FS 49 and DK-AH 269 reduce heart rate by slowing diastolic depolarization rate in the sino-atrial (SA) node, which might originate from the use-dependent blockade of a hyperpolarization-activated current If. A hyperpolarization-activated current Ih, which is present in many types of neurons, is similar to If. We studied the effects of these drugs on Ih in cultured mouse dorsal root ganglion (DRG) neurons. 2. With the whole-cell patch-clamp technique use-dependent block of Ih was observed. The steady-state block following a voltage-clamp pulse train (1-s steps from -38 to -108 mV applied at 0.5 Hz) was dependent on drug concentration and showed an apparent Kd of 0.1 and 0.79 microM with DK AH 269 and UL-FS 49 respectively. 3. The rate of block increased linearly with drug concentration. The rate of recovery from block was, however, much slower compared to cardiac tissue. 4. There was no significant effect of UL-FS 49 on the activation curve. 5. At high concentrations of UL-FS 49 a clear association of the drug with the open channel was observed. 6. When the cell was stimulated at a frequency of 3 Hz, a distinct hyperpolarization was observed in the presence of extracellular Cs+ or when Ih was blocked with UL-FS 49, but not in the absence of Cs+ and UL-FS 49. 7. These results indicate that Ih protects the cell against hyperpolarizations and subsequent inexcitability. The action of the drugs on the hyperpolarization-activated current in cardiac and neuronal tissue show some similarities; however, some pronounced differences indicate that different subtypes of the channel might exist.

Animals↗
PubMed1998

Pelvic-floor therapy in girls with recurrent urinary tract infections and dysfunctional voiding.

OBJECTIVE: To analyse the treatment of girls with recurrent urinary tract infections (UTIs, at least two periods confirmed) and urodynamically confirmed dysfunctional voiding with pelvic-floor therapy. PATIENTS AND METHODS: Forty-two girls with recurrent UTIs were treated prospectively during a study period of 18 months. Training consisted of an individually adapted voiding and drinking schedule, pelvic-floor relaxation biofeedback, instructions on toilet behaviour and biofeedback uroflowmetry; residual urine was estimated by ultrasonography. All the girls received prophylactic antibiotics during treatment and those girls with urodynamically proven detrusor instability (33) received anticholinergics. Therapy was considered successful when the girls remained free of infection with no further prophylactic antibiotics for at least 6 months. RESULTS: Four girls younger than 6 years all suffered nocturnal and diurnal incontinence and two had reflux. Treatment was effective for recurrent UTI in all and the reflux resolved in two. All four girls became dry during the day and one became dry at night. In the 38 girls older than 6 years, the treatment was successful for recurrent UTI in 24 from the out-patient and in all three from the clinical programme. Reflux, which was seen in six of these girls, resolved in five; one girl underwent bilateral reimplantation. Incontinence was treated in all 23 girls with incontinence problems before treatment (four of whom were initially dry). Twelve girls needed a wetting alarm to become dry during the night. In four girls the treatment was effective for recurrent UTI but the incontinence persisted; in seven the treatment was considered unsuccessful as they all had UTIs after treatment; all remained incontinent. Reflux persisted in all four girls in this group who had reflux before treatment. CONCLUSION: The training programme was effective in treating recurrent UTI in 35 of 42 girls (83%). The persistence of incontinence problems is a bad prognostic factor for the recurrence of UTI after the training programme. Pelvic-floor therapy seems a reasonable and meaningful component in the treatment of recurrent UTIs in which detrusor-sphincter dyssynergia plays a role.

Adolescent↗
PubMed1998

Combined use of urinary alpha1-microglobulin and 99mTc DMSA scintigraphy in the diagnosis and follow-up of acute pyelonephritis and cystitis in children.

OBJECTIVES: In the absence of specific symptomatology in children and neurogenic bladder disease patients, the early diagnosis of acute pyelonephritis is a challenge. The aim of the present study was to determine if dimercaptosuccinic acid (DMSA) lesion-positive (acute pyelonephritis) patients have elevated urinary alpha1-microglobulin (alpha1-MG) excretion (no false negatives) and if DMSA lesion-negative (cystitis) patients have normal urinary alpha1-MG excretion (no false positives). METHODS: A selected population of 62 children above 3 months of age with a proven urinary tract infection were administered a DMSA scan. A control scan was performed after the acute phase of the illness, and the diagnosis of pyelonephritis (n = 44) was made retrospectively. The urinary alpha1-MG was determined by immunonephelometry. RESULTS: The urinary alpha1-MG-creatinine ratio was highly sensitive (98%) and specific (100%) and correlated with the DMSA scintigraphy images. Only 1 of the 44 patients with pyelonephritis and all of the cystitis patients (n = 18) had a normal urinary alpha1-MG (<10 mg/g). The drop in absolute DMSA uptake correlated significantly (r = 0. 758, p < 0.001) with the urinary alpha1-MG-creatinine ratio. The urinary alpha1-MG-creatinine ratio was significantly higher (p < 0. 02) in bilateral than in unilateral pyelonephritis. CONCLUSION: DMSA lesion-positive (acute pyelonephritis) patients have elevated urinary alpha1-MG excretion and DMSA lesion-negative (cystitis) patients have normal urinary alpha1-MG excretion.

Acute Disease↗
PubMed1998

Effects of the competitive N-methyl-D-aspartate antagonist CGP 37849 and its ethylester CGP 39551 on N-methyl-D-aspartate-evoked whole-cell currents in cultured spinal neurones and on vestibular stimulation-induced seizures in EL mice.

The competitive N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CAS 127910-31-0, 4-methyl-APPA, CGP 37849) and its ethyl ester (CAS 127910-32-1, CGP 39551) potently block NMDA-evoked whole-cell current on mouse spinal neurones in primary dissociated cell cultures with IC50 (+/- SE) values of 189 +/- 9 nmol/l (CGP 37849) and 2100 +/- 220 nmol/l (CGP 39551), respectively. The compounds dose-dependently blocked vestibular stimulation-induced convulsions in EL mice, 2 h after oral administration, with ED50 (95% CI) values of 135 (78-236) mumol/kg (CGP 37849) and 65 (45-94) mumol/kg (CGP 39551). In male Swiss albino mice, performance in the step-through passive avoidance procedure was dose-dependently impaired with ED50 (95% CI) values of 85 (56-157) mumol/kg (CGP 37849) and 27 (18-42) mumol/kg (CGP 39551). In addition performance of these animals in the rotarod test of motor coordination was impaired, 2 h after oral administration of CGP 39551, with an ED50 (95% CI) of 142 (100-201) mumol/kg. These findings demonstrate anticonvulsant activity in these potent NMDA antagonists after oral administration with CGP 39551 possessing greater relative potency. However, the unfavourable ratio of therapeutic dose versus dose inducing memory or motor impairment supports the prevailing notion that such adverse effects of the presently available compounds preclude the use of NMDA antagonists as long-term therapies.

2-Amino-5-phosphonovalerate↗
PubMed1997

Effect of cAMP and ATP on the hyperpolarization-activated current in mouse dorsal root ganglion neurons.

In mouse dorsal root ganglion (DRG) neurons the activation curve of the hyperpolarization-activated current (Ih) shifted towards depolarized potentials when cAMP was present in the pipette. The relation between the midpoint potential and cAMP concentration could be described by a Hill function with a half-maximal concentration of 0.55 microM cAMP, reflecting a direct action of cAMP on the channel. With 5 mM ATP and a saturating concentration of cAMP an additional shift of the midpoint potential is observed which can be explained by phosphorylation. Application of Rp-cAMPS and Sp-cAMPS support the hypothesis of both a phosphorylation pathway and a direct effect exhibited by these molecules. The bell-shaped curves, relating the time constants for the slow and fast current components to the voltage, shifted towards positive membrane potentials when cAMP and ATP were in the pipette. The fully activated Ih/voltage relation and the reversal potential were not dependent on the presence of cAMP or ATP in the pipette. The mean resting membrane potential of -59 mV, using the perforated-patch configuration, hyperpolarized in the presence of extracellular CsCl. In the whole-cell configuration the resting membrane potential was significantly more negative at 0 microM cAMP (-61 mV) than at 100 microM cAMP (-57 mV). Thus, the activation of Ih, regulated by both the intracellular cAMP and the ATP concentration, may influence the excitability of DRG neurons.

Adenosine Triphosphate↗
PubMed1997

[Differences in the profile of nycthemeral diuresis].

Monosymptomatic enuresis in childhood can be divided in two subtypes by a nycthemeral diuresis profile, including urinary volume and osmolality. The first one is characterized by an abnormal circadian diuresis cycle, responsible for nocturnal polyuria and/or low urinary overnight osmolality, there is a good response to desmopressin; the other one is the so-called cognitive or idiopathic type, which provides a poor response to desmopressin.

Adolescent↗
PubMed1997

[Urination disorders revealing posterior urethral valve: clinical aspects].

One hundred sixty-four boys presenting with voiding dysfunction without any obvious uropathy or neuropathy were enrolled in a prospective study. Nine (5.5%) were suspected to have urethral valves after video-urodynamic assessment, later confirmed by cystoscopy. Those with proven posterior urethral valves were compared to a control group of boys without urethral obstruction. There was no difference in anamnesis nor clinical presentation between the two groups. Even on uroflowmetry the urethral valves were not suspected; only the urodynamic assessment could distinguish the obstructed from the non-obstructed boys. Although there remains controversy about the existence of posterior urethral valves in functional voiding disorders in boys, we could demonstrate that after a complete prospective screening such a rare combination occurs in around 5% of the cases.

Child↗
PubMed1997

Selective block of N-methyl-D-aspartic acid (NMDA)-evoked whole-cell currents in mouse cultured spinal neurones by CGP 40116.

1. CGP 40116 is the active (R)-enantiomer of the most potent N-methyl-D-aspartic acid (NMDA) receptor antagonist presently available: 2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849). In this study, we describe the effect of CGP 40116 on whole-cell currents induced by excitatory amino acids in cultured mouse spinal cord cells by use of the whole-cell patch-clamp technique. 2. We found that application of CGP 40116 in the nM range, concentration-dependently inhibited whole-cell current evoked by 20 microM NMDA in mouse cultured spinal neurones (IC50 +/- s.e. mean 48 +/- 8 nm CGP 40116). 3. The compound appeared to be highly selective for the NMDA current. At concentrations as high 1 microM, currents evoked by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or kainic acid were not affected by CGP 40116. The threshold concentration for antagonism of NMDA-induced responses was 10 nM suggesting a selectivity ratio of > or = 100 fold for NMDA receptors versus AMPA or kainate receptors. 4. CGP 40116 produced a parallel rightward displacement of the NMDA log concentration-current curve indicating competitive antagonism at the transmitter recognition site of the NMDA receptor complex. An apparent dissociation constant for the antagonist was calculated from the displacement of the agonist concentration-current curve: 117 +/- 53 nM CGP 40116 (estimated Kd +/- s.e.). Like other competitive NMDA antagonists, CGP 40116 blocked NMDA-evoked current in a voltage-independent manner.

2-Amino-5-phosphonovalerate↗
PubMed1997

Advantages of HCO3 solution with low sodium concentration over standard lactate solutions for acute peritoneal dialysis.

The aim of this study was to identify the advantages of a bicarbonate solution with a low sodium concentration. Twelve children (3 days-6 years) with acute renal failure (ARF), positive fluid balance, and lactate acidosis (> 40 mg/dL) were treated by automated peritoneal dialysis (APD) with frequent exchanges of small fill volumes of a hypertonic solution. For Day 1 we used PD1/PD4 Dianeal (3.86%) (Baxter). After 24 hours we switched to a HCO3 solution: 38 mmol/L, Na 128 mmol/L. As the control group, we studied retrospectively the last 12 children of the previous period who were treated with APD. The age distribution was 4 days to 4 years. No significant differences were found between the groups for serum creatinine, blood urea nitrogen, and fluid overload (Day 1 to Day 4). Although the values for lactate and Na were not different before the start of the study (Day 1) and after 24 hours of Dianeal (Day 2), they were significantly lower in the study group on Day 4 [HCO3 53 (23-83), Na 148 (137-136) mEq/L] than in the control group [lactate 148 (137-156), Na 154 (142-165) mEq/L]. A low sodium concentration results in higher sodium extraction, which is important for patients with fluid overload. Low sodium concentrations in APD are needed because the peritoneal membrane "sieves" the sodium during short dwells. HCO3 dialysis is a logical choice for patients with lactate acidosis, resulting in a significant lower serum lactate and increase of BE after 48 hours of treatment.

Acute Kidney Injury↗
PubMed1997

New perspectives for PD in acute renal failure related to new catheter techniques and introduction of APD.

Acute renal failure remains a major problem in pediatric intensive care unit (PICU) patients. Although in most handbooks peritoneal dialysis (PD) is still considered to be the first choice for children < 20 kg and there is some evidence that PD may preserve and/or favor recuperation of renal function, most PICU departments are using continuous veno-venous hemofiltration and dialysis or hemodialysis as treatment. The main reasons for this are workload for the PICU nurses, catheter problems, the risk of peritonitis, and limited ultrafiltration. In a retrospective study (1992-1995) in 46 patients (age 3 days to 14 years), automated PD (APD) was the initial treatment in 44 patients. Complications of the Seldinger-placed Cook (pleuropericard) catheter were limited: leakage (1/44); bleeding: n = 0; obstruction or dislocation: n = 4; peritonitis: n = 1 (Candida); ultrafiltration (UF) problems: n = 3. APD in children with acute renal function (ARF) is a good alternative for continuous veno-venous dialysis. Placement of a pigtail (Cook) catheter is a quick (10 min), safe procedure, with low leakage risk. This, together with the low manipulation rate, gives a low peritonitis rate. The use of the cycler makes frequent changes of small volumes possible, resulting in better clearance, good UF, no interference with hemodynamic or respiratory stability, and a reduced workload.

Acute Kidney Injury↗
PubMed1997

Membrano-bulbo-urethral junction stenosis. Posterior urethra obstruction due to extreme caliber disproportion in the male urethra.

OBJECTIVE: Based on 4 cases of infravesical obstruction due to extreme caliber disproportion between the posterior urethra and the penile urethra, a pathophysiological mechanism for this dynamic obstruction is given and endoscopic treatment is described. SUBJECTS: Four cases of membrano-bulbo-urethral junction (MBUJ) stenosis, seen between September 1995 and April 1996, are described. Two boys had previous successful valve resection but still showed extreme ballooning of the posterior urethra. The other 2 boys showed bladder instability on urodynamics and the male variant of the spinning top urethra on voiding cystourethrography (VCUG). RESULTS: All cases were successfully treated by endoscopic incision at the 12 o'clock position of the kink between the posterior and the penile urethra which is seen when the full bladder is expressed. Disproportion in the posterior urethra, seen on VCUG, together with bad urinary flow measured on uroflowmetry raise the suspicion of MBUJ stenosis. CONCLUSION: Although rarely seen, extreme caliber disproportion in the male urethra can cause obstruction. Ballooning of the posterior urethra, caused by urethral valves, bladder instability resisted by voluntary sphincter contraction or congenital posterior urethral dilatation, creates an obstructive kink in the urethra comparable to some obstructions in ureteropelvic junction stenosis. If suspicion of such a form of obstruction arises, cystoscopy during pressure on the full bladder is mandatory in order to see the obstruction, descending as a membrane from the vault of the urethra.

Adolescent↗