Chronic L-DOPA administration increases the firing rate but does not reverse enhanced slow frequency oscillatory activity and synchronization in substantia nigra pars reticulata neurons from 6-hydroxydopamine-lesioned rats.

The pathophysiology of Parkinson's disease (PD) and of L-DOPA-induced dyskinesia (LID) is associated with dysfunctional neuronal activity in several nuclei of the basal ganglia. Moreover, high levels of oscillatory activity and synchronization have also been described in both intra- and inter-basal ganglia nuclei and the cerebral cortex. However, the relevance of these alterations in the motor symptomatology related to Parkinsonism and LID is not fully understood. Recently, we have shown that subthalamic neuronal activity correlates with axial abnormal movements and that a subthalamic nucleus (STN) lesion partially reduces LID severity as well as the expression of some striatal molecular modifications. The aim of the present study was to assess, through single-unit extracellular recording techniques under urethane anaesthesia, neuronal activity of the substantia nigra pars reticulata (SNr) and its relationship with LID and STN hyperactivity together with oscillatory and synchronization between these nuclei and the cerebral cortex in 6-OHDA-lesioned and dyskinetic rats. Twenty-four hours after the last injection of L-DOPA the firing rate and the inhibitory response to an acute challenge of L-DOPA of SNr neurons from dyskinetic animals were increased with respect to those found in intact and 6-OHDA-lesioned rats. Moreover, there was a significant correlation between the mean firing rate of SNr neurons and the severity of the abnormal movements (limb and orolingual subtypes). There was also a significant correlation between the firing activity of SNr and STN neurons recorded from dyskinetic rats. In addition, low frequency band oscillatory activity and synchronization both within the SNr or STN and with the cerebral cortex were enhanced in 6-OHDA-lesioned animals and not or slightly affected by chronic treatment with L-DOPA. Altogether, these results indicate that neuronal SNr firing activity is relevant in dyskinesia and may be driven by STN hyperactivity. Conversely, low frequency oscillatory activity and synchronization seem to be more important in PD because they are not influenced by prolonged L-DOPA administration.

Identification of potentially irritating intravenous medications.

AIMS: To identify commonly used intravenous drugs that may produce endothelial damage. METHODS: An experimental research study was performed using a sample of 62 intravenous drugs commonly used in emergency care, pH and osmolarity were measured. Subsequently, based on these values, the theoretical capacity to cause irritation or endovascular damage was determined and classified as high, moderate, and low. RESULTS: Samples from 19 drugs for fluid therapy, 21 antibiotics and 22 drugs for intravenous use were studied. Glucose solutions, sodium bicarbonate 1M and mannitol 10% showed a high capacity to cause venous irritation. Vancomycin, ciprofloxacin, amiodarone, haloperidol, and labetalol solution presented a high capacity for irritation based on their acidic pH. The antibiotics, dexketoprofen, diazepam, digoxin, etomidate, phenytoin, levetiracetam and metamizole also showed high osmotic values in their reconstituted or undiluted presentations. Moreover, osmolarity of diazepam, digoxin and phenytoin remained high despite being diluted in 100 ml of saline. CONCLUSIONS: Knowing the pH and osmolarity of intravenous drugs allows their capacity to cause endothelial damage to be assessed. The use of comprehensive tables based on the chemical properties of the drugs can be a useful tool to help prevent chemically-induced phlebitis.

Consensus and recommendations on vaginal-cuff Brachytherapy of the Spanish Brachytherapy Groups of SEOR and SEFM.

PURPOSE/OBJECTIVE(S): On October 5, 2018, a meeting of the Spanish Society of Radiation Oncology (SEOR) Brachytherapy Group was held, in collaboration with the Spanish Society of Medical Physics (SEFM), with the aim of preparing a consensus document on postoperative vaginal-cuff brachytherapy (VCBT). MATERIALS/METHODS: A survey including 42 questions was sent to Spanish Radiation Oncology Centres before the meeting. The survey items included: experience in VCBT, technique indications, previous patient preparation, applicator type, implant procedure, computerized tomography (CT) simulation, definition of target volumes and organs at risk (OAR), dose prescription, fractionation, treatment planning, dosimetric parameters and constraints to OAR. Thirty-three centres answered the survey. Statistical analysis of the survey considered that there was consensus when there was ≥ 85% of agreement related to a survey item, otherwise an item with < 85% of agreement would be discussed during the meeting to reach consensus. RESULTS: The results of the survey are reported here. The mean number of patients treated per centre in 2017 was 52 ± 41 (range 7-175), and the mean number of procedures per centre was 175 ± 150 (range 24-701).There was consensus on: the indications, applicator type, the OAR to be considered, the prescription point, standardisation and dosimetric quality parameters. There was no consensus on: patient preparation for the implant, the need for performing CT simulation and the frequency, the length of the vagina to be treated, if CTV should be delimited, the definition of the clinical target volume, fractionation, overall EQD2, active source length, separation between dwelling stepping source positions, if considering the uniformity/maximum values for dwelling stepping sources, the optimization mode, and the limiting doses to the OAR. After presenting the results of the survey, the consensus meeting discussion focused on the issues for which there was no consensus. CONCLUSION: A consensus document on postoperative VCBT of the Spanish Brachytherapy Groups of SEOR-SEFM was elaborated.

Acute L-DOPA administration reverses changes in firing pattern and low frequency oscillatory activity in the entopeduncular nucleus from long term L-DOPA treated 6-OHDA-lesioned rats.

The pathophysiology of Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID) is associated with aberrant neuronal activity and abnormal high levels of oscillatory activity and synchronization in several basal ganglia nuclei and the cortex. Previously, we have shown that the firing activity of neurons in the substantia nigra pars reticulata (SNr) is relevant in dyskinesia and may be driven by subthalamic nucleus (STN) hyperactivity. Conversely, low frequency oscillatory activity and synchronization in these structures seem to be more important in PD because they are not influenced by prolonged L-DOPA administration. The aim of the present study was to assess (through single-unit extracellular recording techniques under urethane anaesthesia) the neuronal activity of the entopeduncular nucleus (EPN) and its relationship with LID and STN hyperactivity, together with the oscillatory activity and synchronization between these nuclei and the cerebral cortex in 6-OHDA-lesioned rats that received long term L-DOPA treatment (or not). Twenty-four hours after the last L-DOPA injection the firing activity of EPN neurons in long term L-DOPA treated 6-OHDA-lesioned rats was more irregular and bursting compared to sham rats, being those alterations partially reversed by the acute challenge of L-DOPA. No correlation between EPN neurons firing activity and abnormal involuntary movements score was found. However, there was a significant correlation between the firing activity parameters of EPN and STN neurons recorded from long term L-DOPA treated 6-OHDA-lesioned rats. Low frequency oscillatory activity and synchronization both within the EPN and with the cerebral cortex were enhanced in 6-OHDA-lesioned animals. These changes were reversed by the acute L-DOPA challenge only in long term L-DOPA treated 6-OHDA-lesioned rats. Altogether, these results obtained from long term L-DOPA treated 6-OHDA-lesioned rats suggest (1) a likely relationship between STN and EPN firing patterns and spiking phases induced by changes after prolonged L-DOPA administration and (2) that the effect of L-DOPA on the firing pattern, low frequency oscillatory activity and synchronization in the EPN may have a relevant role in LID.

The acute and long-term L-DOPA effects are independent from changes in the activity of dorsal raphe serotonergic neurons in 6-OHDA lesioned rats.

BACKGROUND AND PURPOSE: L-DOPA is still the most efficacious pharmacological treatment for Parkinson's disease. However, in the majority of patients receiving long-term therapy with L-DOPA, its efficacy is compromised by motor complications, notably L-DOPA-induced dyskinesia. Evidence suggests that the serotonergic system is involved in the therapeutic and the side effects of L-DOPA. Here, we investigate if long-term L-DOPA treatment alters the activity of the dorsal raphe nucleus (DRN) and its responses to serotonergic drugs. EXPERIMENTAL APPROACH: We measured the responses of serotonergic neurons to acute and chronic L-DOPA treatment using in vivo electrophysiological single unit-extracellular recordings in the 6-OHDA-lesion rat model of Parkinson's disease. KEY RESULTS: The results showed that neither acute nor chronic L-DOPA administration (6 mg·kg(-1)  s.c.) altered the properties of serotonergic-like neurons. Furthermore, no correlation was found between the activity of these neurons and the magnitude of L-DOPA-induced dyskinesia. In dyskinetic rats, the inhibitory response induced by the 5-HT1A receptor agonist 8-OH-DPAT (0.0625-16 µg·kg(-1) , i.v.) was preserved. Nonetheless, L-DOPA impaired the ability of the serotonin reuptake inhibitor fluoxetine (0.125-8 mg·kg(-1) , i.v) to inhibit DRN neuron firing rate in dyskinetic animals. CONCLUSIONS AND IMPLICATIONS: Although serotonergic neurons are involved in the dopaminergic effects of L-DOPA, we provide evidence that the effect of L-DOPA is not related to changes of the activity of DRN neurons. Rather, L-DOPA might reduce the efficacy of drugs that normally enhance the extracellular levels of serotonin. LINKED ARTICLES: This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc.

Buspirone requires the intact nigrostriatal pathway to reduce the activity of the subthalamic nucleus via 5-HT1A receptors.

The most effective treatment for Parkinson's disease (PD), l-DOPA, induces dyskinesia after prolonged use. We have previously shown that in 6-hydroxydopamine (6-OHDA) lesioned rats rendered dyskinetic by prolonged l-DOPA administration, lesion of the subthalamic nucleus (STN) reduces not only dyskinesias but also buspirone antidyskinetic effect. This study examined the effect of buspirone on STN neuron activity. Cell-attached recordings in parasagittal slices from naïve rats showed that whilst serotonin excited the majority of STN neurons, buspirone showed an inhibitory main effect but only in 27% of the studied cells which was prevented by the 5-HT1A receptor selective antagonist WAY-100635. Conversely, single-unit extracellular recordings were performed in vivo on STN neurons from four different groups, i.e., control, chronically treated with l-DOPA, 6-OHDA lesioned and lesioned treated with l-DOPA (dyskinetic) rats. In control animals, systemic-buspirone administration decreased the firing rate in a dose-dependent manner in every cell studied. This effect, prevented by WAY-100635, was absent in 6-OHDA lesioned rats and was not modified by prolonged l-DOPA administration. Altogether, buspirone in vivo reduces consistently the firing rate of the STN neurons through 5-HT1A receptors whereas ex vivo buspirone seems to affect only a small population of STN neurons. Furthermore, the lack of effect of buspirone in 6-OHDA lesioned rats, suggests the requirement of not only the activation of 5-HT1A receptors but also an intact nigrostriatal pathway for buspirone to inhibit the STN activity.

Intranasal Administration of chitosan-Coated Nanostructured Lipid Carriers Loaded with GDNF Improves Behavioral and Histological Recovery in a Partial Lesion Model of Parkinson's Disease.

Parkinson's disease (PD) is the second most frequent neurodegenerative disorder, but current therapies are only symptomatic. A promising alternative to address the neurodegenerative process is the use of neurotrophic factors, such as the glial cell-derived neurotrophic factor (GDNF). However, its clinical use has been limited due to its short half-life and rapid degradation after in vivo administration, in addition to difficulties in crossing the blood-brain barrier (BBB). This barrier is a limiting factor in brain drug development, making the future progression of neurotherapeutics difficult. In the past few years, intranasal drug delivery has appeared as an alternative non-invasive administration route to bypass the BBB and target drugs directly to the CNS. Thus, the aim of this work was to study the in vivo neuroprotective effect of intranasally administered GDNF, encapsulated in chitosan-coated nanostructured lipid carrier (CS-NLC-GDNF), in a 6-OHDA partially lesioned rat model. The developed CS-NLC-GDNF showed a particle size of approximately 130 nm and high encapsulation efficiency. The in vitro study in PC-12 cells demonstrated the ability of the encapsulated GDNF to protect these cells against 6-OHDA toxin. After two weeks of daily intranasal administration of treatments, the administration of CS-NLC-GDNF achieved a behavioral improvement in rats, as well as a significant improvement in both the density of TH+ fibres in the striatum and the TH+ neuronal density in the SN. Thus, it can be concluded that the nose-to-brain delivery of CS-NLC-GDNF could be a promising therapy for the treatment of PD.

Comparative study of basiliximab treatment in lung transplantation.

OBJECTIVE: This study compared the incidence of acute or chronic rejection and adverse events in lung transplant patients receiving induction basiliximab versus controls not receiving treatment. MATERIALS AND METHODS: Basiliximab was administered to 15 patients with impaired renal function, advanced age, or high surgical risk, (group I). The mean age was 48.9 years; nine were double-lung and six single-lung grafts. They were compared to 13 lung transplants performed in 2001 (mean age 43.6 years, 11 double lung and two single lung [group II]). RESULTS: The incidence of acute rejection was 13.3% in group I versus 38.5% in group II (P = .19, OR 4.06), with chronic rejection in 20% and 38.5% of cases, respectively (P = .4, OR 2.5). No significant differences were observed in the incidence of infections or malignancies. Nor were there any direct adverse events due to the administration of the drug. The estimated 2-year survival was 80% for group I and 54% for group II (P = .14). CONCLUSIONS: Basiliximab has a trend to reduce the rate of acute and chronic rejection in lung transplant recipients, with no increased incidence of infections or malignancies. The 2-year survival for patients treated with basiliximab was better than the control group, despite including high risk transplant patients.

Basiliximab in lung transplantation: preliminary experience.

BACKGROUND: Basiliximab is a chimeric anti-interleukin-2 monoclonal antibody that has shown safety and efficacy in the prophylaxis of acute organ rejection in renal, liver, heart, and kidney-pancreas transplantation (Tx). The aim of this study was to present our initial experience with the use of Basiliximab in lung Tx. METHODS: Basiliximab (2 doses of 20 mg on day 0 and day 4) was administered to 16 patients treated with cyclosporine, azathioprine, and steroids between September 13, 2001 and August 26, 2003, including 12 men and 4 women patients with a mean age of 56.5 years (range, 19-69). The indication for use in transplantations were: reduced renal function (n = 14), post-Tx acute renal failure (n = 1) and steroid-resistant acute rejection (n = 1). Eight double-lung and eight single-lung Tx were performed for emphysema (n = 6), idiopathic pulmonary fibrosis (n = 7), silicosis (n = 2), and cystic fibrosis retransplantation (n = 1). RESULTS: The incidence of acute rejection was 16.6% (2 patients). Infections included cytomegalovirus (CMV) 33.3% (n = 4), bacterial 16.6% (n = 2), and fungal 8.3% (n = 1). Two patients died in the postoperative period and another at 3 months. There was no reaction to the medicine, and no malignancies or Bronchiolitis Obliterans Syndrome (BOS) during a follow-up period of more than 1 year in 10 patients. CONCLUSION: Basiliximab appeared to reduce the incidence of acute organ rejection and showed a good safety profile in terms of infections and adverse events.

Experimental antireflux intestinal valve.

A reflux-preventing valve was obtained by invaginating a 3.5 to 4.5 cm segment of small bowel into the distal lumen, after removing the seromuscular layers at both ends of the segment of bowel. Antiperistaltic pressure resistance, measured at regular intervals during 6 months, showed valves with competence equal or superior to the ileocecal valve. The blood supply to the intussuscepted segment must be carefully preserved.

[Uropediatrics. Update and controversies]. / Uropediatría. Actualización y controversias.

On the occasion of the 25 Anniversary of the official Journal of the Spanish Urological Association, we do an overall view of Spanish Pediatric Urology (U.P.) at present time, and we perform an updating of the most prevalent and controversial aspects in U.P., as the foetal Urology, the vesicoureteral reflux and the pyelo-ureteral stenosis.

Altered neuronal activity and differential sensitivity to acute antidepressants of locus coeruleus and dorsal raphe nucleus in Wistar Kyoto rats: a comparative study with Sprague Dawley and Wistar rats.

The Wistar Kyoto rat (WKY) has been proposed as an animal model of depression. The noradrenergic nucleus, locus coeruleus (LC) and the serotonergic nucleus, dorsal raphe (DRN) have been widely implicated in the ethiopathology of this disease. Thus, the goal of the present study was to investigate in vivo the electrophysiological properties of LC and DRN neurons from WKY rats, using single-unit extracellular techniques. Wistar (Wis) and Sprague Dawley (SD) rats were used as control strains. In the LC from WKY rats the basal firing rate was higher than that obtained in the Wis and SD strain, and burst firing activity also was greater compared to that in Wis strain but not in SD. The sensitivity of LC neurons to the inhibitory effect of the α2-adrenoceptor agonist, clonidine and the antidepressant reboxetine was lower in WKY rats compared to Wis, but not SD. Regarding DRN neurons, in WKY rats burst activity was lower than that obtained in Wis and SD rats, although no differences were observed in other firing parameters. Interestingly, while the sensitivity of DRN neurons to the inhibitory effect of the 5-HT1A receptor agonist, 8-OH-DPAT was lower in the WKY strain, the antidepressant fluoxetine had a greater inhibitory potency in this rat strain compared to that recorded in the Wis group. Overall, these results point out important electrophysiological differences regarding noradrenergic and serotonergic systems between Wis and WKY rats, supporting the utility of the WKY rat as an important tool in the research of cellular basis of depression.

Modulation of the subthalamic nucleus activity by serotonergic agents and fluoxetine administration.

RATIONALE: Within the basal ganglia, the subthalamic nucleus (STN) is the only glutamatergic structure and occupies a central position in the indirect pathway. In rat, the STN receives serotonergic input from the dorsal raphe nucleus and expresses serotonergic receptors. OBJECTIVE: This study examined the consequences of serotonergic neurotransmission modulation on STN neuron activity. METHODS: In vivo single-unit extracellular recordings, HPLC determination, and rotarod and bar test were performed in control, 4-chloro-DL-phenylalanine methyl ester hydrochloride- (pCPA, a serotonin synthesis inhibitor) and chronically fluoxetine-treated rats. RESULTS: The pCPA treatment and the administration of serotonin (5-HT) receptor antagonists increased number of bursting neurons in the STN. The systemic administration of the 5-HT(1A) agonist, 8-OH-DPAT, decreased the firing rate and increased the coefficient of variation of STN neurons in pCPA-treated rats but not in control animals. Additionally, microinjection of 8-OH-DPAT into the STN reduced the firing rate of STN neurons, while microinjection of the 5-HT(2C) agonist, Ro 60-0175, increased the firing rate in both control and fluoxetine-treated animals. Finally, the fluoxetine challenge increased the firing rate of STN neurons in fluoxetine-treated rats and induced catalepsy. CONCLUSIONS: Our results indicate that the depletion and the blockage of 5-HT modify STN neuron firing pattern. STN neuron activity is under the control of 5-HT(1A) and 5-HT(2C) receptors located both inside and outside the STN. Finally, fluoxetine increases STN neuron activity in chronically fluoxetine-treated rats, which may explain the role of this nucleus in fluoxetine-induced extrapyramidal side effects.

L-DOPA modifies the antidepressant-like effects of reboxetine and fluoxetine in rats.

Nowadays the most widely used antidepressants are selective serotonin reuptake inhibitors (SSRI) or noradrenaline reuptake inhibitors (NRI), however, these take four to eight weeks to exert their effects and each drug is efficacious only in 60-70% of patients. In an attempt to improve the efficacy of antidepressants, new drugs that also modify dopamine levels are being developed. The aim of this study was to investigate the impact of l-DOPA administration on the effect elicited by antidepressants on serotonergic and noradrenergic neurotransmission. To this end, single-unit extracellular recordings of the noradrenergic nucleus, locus coeruleus (LC), and the serotonergic nucleus, dorsal raphe (DRN) combined with behavioural approaches were performed. l-DOPA did not modify the basal neuronal activity in either the LC or the DRN or induce any change in the modified forced swimming test. However, l-DOPA enhanced the neuronal response to reboxetine in the LC and increased its antidepressant-like effects but counteracted the effect of fluoxetine on neurons in the LC and decreased its antidepressant-like effect. The sensitivity of neurons in the DRN to reboxetine and fluoxetine was not altered by the administration of l-DOPA. Taken together, these results indicate that l-DOPA modifies the effect of SSRI and NRI antidepressants in opposing ways.

A comprehensive analysis of the effect of DSP4 on the locus coeruleus noradrenergic system in the rat.

Degeneration of the noradrenergic neurons in the locus coeruleus (LC) is a major component of Alzheimer's (AD) and Parkinson's disease (PD), but the consequence of noradrenergic neuronal loss has different effects on the surviving neurons in the two disorders. Therefore, understanding the consequence of noradrenergic neuronal loss is important in determining the role of this neurotransmitter in these neurodegenerative disorders. The goal of the study was to determine if the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) could be used as a model for either (or both) AD or PD. Rats were administered DSP4 and sacrificed 3 days 2 weeks and 3 months later. DSP4-treatment resulted in a rapid, though transient reduction in norepinephrine (NE) and NE transporter (NET) in many brain regions receiving variable innervation from the LC. Alpha(1)-adrenoreceptors binding site concentrations were unchanged in all brain regions at all three time points. However, an increase in alpha(2)-AR was observed in many different brain regions 2 weeks and 3 months after DSP4. These changes observed in forebrain regions occurred without a loss in LC noradrenergic neurons. Expression of synthesizing enzymes or NET did not change in amount of expression/neuron despite the reduction in NE tissue content and NET binding site concentrations at early time points, suggesting no compensatory response. In addition, DSP4 did not affect basal activity of LC at any time point in anesthetized animals, but 2 weeks after DSP4 there is a significant increase in irregular firing of noradrenergic neurons. These data indicate that DSP4 is not a selective LC noradrenergic neurotoxin, but does affect noradrenergic neuron terminals locally, as evident by the changes in transmitter and markers at terminal regions. However, since DSP4 did not result in a loss of noradrenergic neurons, it is not considered an adequate model for noradrenergic neuronal loss observed in AD and PD.

alpha(2)-Adrenoceptors mediate the acute inhibitory effect of fluoxetine on locus coeruleus noradrenergic neurons.

So far, the mechanisms underlying the action of selective serotonin reuptake inhibitors, such as fluoxetine, are not completely understood. Thus, to clarify if fluoxetine has any effect on noradrenergic transmission, we measured the spontaneous firing rate of noradrenergic neurons in the locus coeruleus both in vivo and in vitro using single-unit extracellular recordings. In anesthetized rats, fluoxetine (2.5-20 mg/kg, i.v.) reduced the firing rate in a dose-dependent manner, reaching a maximal inhibition of 55 +/- 5% with respect to the basal value. This effect was not only completely reversed by the alpha(2)-adrenoceptor antagonist, RX 821002 (0.2 mg/kg, i.v.), but also prevented by previous application of both idazoxan (0.05 and 0.1 mg/kg, i.v.) and RX 821002 (6.25 microg/kg, i.v). Furthermore, when noradrenaline was depleted from axon terminals by means of the injection of alpha-methyl-DL-tyrosine (250 mg/kg, i.p.) 24 h prior to the experiment, fluoxetine failed to inhibit locus coeruleus activity. In rat brain slices, perfusion with fluoxetine (100 microM for 5 min) did not modify the firing rate of locus coeruleus neurons (n = 7). We conclude that fluoxetine inhibits locus coeruleus neurons in vivo through a mechanism involving noradrenaline interacting with alpha(2)-adrenoceptors. However, the lack of effect on brain slices would seem to indicate that afferents to the nucleus may be involved in the observed inhibitory effect.

Polyorchidism: an exceptional case of three homolateral testes.

Polyorchidism is an uncommon congenital anomaly defined as the presence of more than two histologically proved testes. The present case of polyorchidism was discovered casually in an 11-year-old boy while performing an orchiopexy. Three testes were found on the left side; we have been unable to find this exceptional anomaly previously published in the medical literature.

Trospium chloride for the treatment of detrusor instability in children.

PURPOSE: We assessed the efficacy and most appropriate dosage of trospium chloride (TCl) for managing bladder instability in children as compared with a placebo. MATERIALS AND METHODS: A total of 58 patients with bladder instability were allocated at random to 1 of 5 groups-10, 15, 20 or 25 mg TCl, or placebo administered daily in a multicenter, randomized, single-blind clinical study. Patients were treated for 21 days, and current symptoms, voiding diary and urodynamic values were collected at the beginning and end of the treatment period. All adverse events were recorded at the last visit. RESULTS: Of 50 patients treated with TCl 41 (82%) had a positive therapeutic result (excellent, good or fair) versus only 3 of 8 patients with improvement in the placebo group (37.5%, p = 0.006). In all responding patients clinical symptoms either resolved or decreased markedly, and in 37 (74%) this improvement was accompanied by urodynamic improvement. In these 37 children the average number of uninhibited contractions decreased by 54.3% (p <0.0001) and the volume at first contraction increased by 71.4% (p = 0.001). There were no statistically significant differences with regard to therapeutic efficacy between TCl dosages. Fourteen patients (9 with TCl, 5 with placebo) showed no clinical improvement, although some had improved urodynamic parameters. Furthermore, TCl was well tolerated with few patients (10%) experiencing adverse effects. CONCLUSIONS: Trospium chloride (10 to 25 mg total daily dosage, split into 2 doses) is an effective option for the management of detrusor instability in children.