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Fifty patients with PWDHD were randomized depending on their visiting sequence into two groups, the 30 patients in the treatment group treated with HXD and the 20 in the control group treated with Domperidone. The therapeutic course for both groups was 2 weeks. Besides, a normal control group consisting of 30 healthy volunteers was set up. The changes of tongue fur, grade of major syndromes in different groups were observed and scored before and after treatment to evaluate the therapeutic effectiveness, and the apoptotic index (AI) was estimated using TUNEL technique.
Twenty consecutive patients with SSc reporting esophageal symptoms underwent high-resolution manometry before and 30 minutes after administration of buspirone (10 mg). Ten other patients received domperidone (10 mg) and served as control group. Changes in LES resting and residual pressure, amplitude, duration, and velocity of distal esophageal body contractions were examined.
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Previous studies reported the existence of both D1- and D2-like receptors in the cortical collecting duct (CCD). However, especially with regard to natriuresis, it remains controversial. In the present study, rabbit CCD was perfused to characterize the receptor subtypes responsible for the tubular actions. Basolateral dopamine (DA) induced a dose-dependent depolarization of transepithelial voltage. Basolateral domperidone, a D2-like receptor antagonist, abolished depolarization, whereas SKF-81297, a D1-like receptor agonist, showed no significant change. In addition, bromocriptine, a D2-like receptor agonist, also caused depolarization, whereas SKF-81297, a D1-like receptor agonist, did not depolarize significantly. Moreover, RBI-257, a D4-specific antagonist, reversed the basolateral DA-induced depolarization. In contrast to the basolateral side, luminal DA caused depolarization via a D1-like receptor; however the change was less than that for basolateral DA. For further evaluation, 22Na+ flux (J(Na)) was measured to confirm the effect of DA on Na+ transport. Basolateral DA also caused a suppression of J(Na), and this reaction was abolished by domperidone. These results suggested that the basolateral D2-like receptor is mainly responsible for the natriuretic action of DA in rabbit CCD.
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Thirty patients with duodenal ulcer in remission running in combination with gastroesophageal reflux disease (GERD) were divided into two groups. Patients of group 1 received medication (omeprasol 20 mg twice a day, motilium 10 mg 3 times a day) and mineral water Klyuchi (200 ml 3 times a day). Patients of group 2 received the same medication but no mineral water. The efficacy of the treatment was assessed by the data obtained at esophagogastroduodenofibroscopy, morphological study of gastric and esophageal biopsies, 24-h pH-metry of the esophagus and the stomach. The results suggest that the addition of mineral water Klyuchi to standard medication of GERD shortens correction of clinical, endoscopic and morphological manifestations of the disease.
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The immunocytochemical study revealed that the major component of the rat retinal cultures was neurons including amacrine cells. The electrophysiologic study using patch-clamp techniques demonstrated that exposure to NMDA-induced currents with properties characteristic of those recorded in the brain. Brief exposure of these neurons to glutamate or NMDA induced delayed cell death. Glutamate neurotoxicity was prevented by the application of dopamine and forskolin. The protective action of dopamine was antagonized by a D1 receptor antagonist (SCH 23390) but not by D2 receptor antagonists (domperidone and sulpiride). A D1 receptor agonist (SKF 38393) protected glutamate-induced neurotoxicity in a concentration-dependent manner, whereas a D2 receptor agonist (quinpirole) did not affect it.
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C-1300 murine neuroblastoma ( MNB ) contains the catecholamine biosynthetic pathway. This study investigated manipulation of this pathway for effects on cell growth and survival in tumor-bearing mice, and to correlate these findings with specific membrane-bound dopamine-binding activity. The dopamine antagonists domperidone, pimozide, and spiroperidol inhibited macromolecular synthesis in vitro as demonstrated by decreased [3H]TdR and [14C]leu incorporation in a dose-response fashion; 56, 49, and 43% inhibition was noted at 10(-6) M concentration of each drug, respectively, with no loss of cell viability. Dopamine agonists showed no significant inhibition. Scatchard analysis of dopamine binding was consistent with a single class of receptor sites with a mean concentration of 13.2 +/- 2.0 pmole/g wet weight of tissue and mean dissociation constant (Kd) = 0.69 +/- 0.38 nM, compared to a mean receptor concentration of 28.1 +/- 5.2 pmole/g wet weight of tissue and Kd = 0.38 +/- 0.09 nM in receptor-rich dog caudate nucleus, the normal control. A/J mice injected with 1 X 10(6) tumor cells and treated with daily pimozide or domperidone had a significant increase in disease-free survival when compared to controls (15 versus 8.5 days, P less than 0.001) as well as a significant increase in overall survival (35 versus 25 days, P less than 0.001). These data suggest that dopamine antagonists inhibit macromolecular synthesis in the C-1300 MNB . The inhibition of MNB tumor growth in vivo by dopamine antagonists suggests a specific chemotherapeutic approach to neuroblastoma, possibly mediated by dopamine receptors.
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The aim of the study was to investigate whether or not the development of hypertension is influenced by chronic treatment with bromocriptine and/or domperidone. Rats treated with DOCA-salt were divided into 4 groups: control with vehicle, bromocriptine, bromocriptine with domperidone, and domperidone. Increased blood pressure by DOCA-salt treatment was significantly suppressed by treatment with bromocriptine and this bromocriptine suppression was significantly blocked by treatment with domperidone. Increased urinary excretion of norepinephrine by DOCA-salt treatment was significantly suppressed by bromocriptine and the inhibiting effect of bromocriptine disappeared with domperidone. In the four groups of rats, there were significant correlations between systolic blood pressure and urinary excretion of norepinephrine, systolic blood pressure and urinary excretion of epinephrine, and urinary excretion of dopamine and sodium. These results suggest that the chronic effect of bromocriptine is to suppress development of DOCA-salt hypertension, mainly through peripheral mechanisms which are involved in the decreased release of norepinephrine.
When developing an LC-MS/MS-method matrix effects are a major issue. The effect of co-eluting compounds arising from the matrix can result in signal enhancement or suppression. During method development much attention should be paid to diminish matrix effects as much as possible. The present work evaluates matrix effects from aqueous environmental samples in the simultaneous analysis of a group of nine specific pharmaceuticals with LC-ESI/MS/MS: flubendazole, propiconazole, pipamperone, cinnarizine, ketoconazole, miconazole, rabeprazole, itraconazole and domperidone. Solutions to diminish signal suppression were examined: optimisation of the sample preparation, decrease of the flow rate, and the use of appropriate internal standards. Several SPE-stationary phases were tested in view of retention of the analytes: Oasis HLB, C8, Phenyl, Strata X-polymer RP sorbent and Strata X-polymeric SCX/RP sorbent. Oasis HLB showed the best retention for all analytes. The Oasis HLB SPE-method was optimised, but analyses showed high matrix suppression. Therefore, a second SPE-method, on a phenyl stationary phase (the second best option), was also optimised. A comparison of the matrix effect was made between the two procedures: the phenyl-method was less subject to matrix effects, however, the average matrix effect (ME%) of 46% indicated that matrix effects where still present. Several optimisation options for the phenyl-method were evaluated: addition of a ferric nitrate solution before extraction, application of an alkaline wash step, and use of a second SPE-cartridge, either a NH2-column or a florisil column. A more efficient sample clean-up was achieved by applying the extract after extraction on the phenyl column and after dilution with chloroform, onto a NH2-column (average ME%: 53%). In addition, applying a post-column split (1:5), further reduced matrix effects (average ME%: 65%). Labelled internal standards are the best way to tackle matrix effects, but no such internal standards were commercially available for the analytes of interest. The thorough search and application of four internal standards (structural analogues) was beneficial and compensates the matrix effect partially (average ME%: 83%). In an attempt to reduce the analysis time Speedisk phenyl columns were applied. Under these conditions matrix effects decreased even more while recoveries were between 91 and 109%. Different kinds of surface water samples were analyzed, and different matrix effects were observed. For this reason, standard addition will be used to perform quantitative analysis.
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The authors of this article present a case of diabetic gastroparesis, initially diagnosed as anorexia nervosa. They compare the symptoms and signs of diabetic gastroparesis with the diagnostic criteria for anorexia nervosa and discuss treatment with domperidone.
1. Intracerebroventricular (IVT) administration of rat atrial natriuretic factor (ANF) (99-126) to conscious male hydrated rats induces a dose-dependent increase in urine and sodium excretion. The possible involvement of brain dopaminergic system in the IVT-ANF-induced diuresis and natriuresis was evaluated. 2. Central sympathectomy (6-OHDA, 250 micrograms/5 microliters, IVT; 72 and 48 hr before IVT-ANF) inhibited both the diuretic and the natriuretic action of centrally administered ANF, suggesting that in the brain ANF requires the integrity of central noradrenergic and/or dopaminergic systems function for its actions. 3. Intracerebroventricular injection of haloperidol and intragastric administration of domperidone prevent the diuretic and natriuretic response to centrally administered ANF. 4. Our data suggest a neuromodulatory action of ANF within the brain and demonstrate an interaction of the peptide with brain dopaminergic systems.
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Itraconazole significantly increased plasma domperidone concentrations. The interaction is probably mainly due to a reduced first pass elimination by inhibition of CYP3A and/or MDR1. The clinical significance of the altered relationship between domperidone concentrations and prolactin levels caused by itraconazole is still to be determined.
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The effect of metoclopramide and domperidone, two dopamine antagonists, administered to cirrhotic patients with ascites and secondary hyperaldosteronism, was examined to evaluate the changes in plasma aldosterone levels and in spironolactone-induced diuresis. In 15 patients with ascites and secondary hyperaldosteronism, the intravenous administration of 10 mg metoclopramide significantly increased plasma aldosterone levels (23%, p less than 0.01). This effect was observed when an equivalent dose of domperidone was administered. In 20 ascitic patients treated with spironolactone (300 mg per day), the administration of metoclopramide (20 mg) significantly reduced urinary output (24%, p less than 0.001) and urinary sodium (35%, p less than 0.001) while simultaneously increasing urinary potassium (24%, p less than 0.001) and plasma aldosterone (40%, p less than 0.001). This effect was not observed with domperidone in an equivalent dose. Therefore, it is recommended that metoclopramide should be avoided during diuretic therapy in cirrhotic patients with ascites. In these circumstances, domperidone is preferred.
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The efficacy of prokinetic agents in functional (nonulcer) dyspepsia has been questioned based on recent trial results. We performed a meta-analysis to determine the efficacy of cisapride and domperidone in functional dyspepsia.
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Two groups of adult female wallabies were maintained in photoperiod-controlled rooms from June 1987 until August 1988. Group SSH was held on summer solstice photoperiods throughout the experiment; group SN was subjected to weekly stepwise simulated natural changes in photoperiod. Plasma melatonin concentrations reflected photoperiod with high concentrations during the dark phase in both groups. Group SN wallabies commenced oestrous cyclicity on 21 July (+/- 19 days, n = 6) entered reproductive quiescence on 14 February (+/- 10 days, n = 5) and recommenced cycling on 8 June (+/- 3 days, n = 4). Group SSH wallabies began cycling on 27 July (+/- 9 days, n = 7) at a time that was not significantly different from that of group SN. Three out of five of group SSH exhibited a spontaneous period of reproductive quiescence of between 59 and 70 days commencing between 3 December and 25 February. There was a highly significant difference between the transient plasma prolactin response to a dopamine antagonist during cycling and quiescent periods in both groups (P < 0.001) such that the response was increased during periods of quiescence. Our data support the hypothesis that prolactin is involved in the control of seasonal quiescence in the female Bennett's wallaby and demonstrate that spontaneous changes in reproductive state and prolactin can occur when animals are maintained on unchanging long photoperiods.
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The results indicate that in man dopamine D2-like receptors are involved in the renal haemodynamic response to amino acid infusion. Whether dopamine D2-like receptor blockade diminishes glomerular hyperfiltration in pathological states requires clinical investigations.
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Sixty-three patients with FD were randomly assigned to two groups, 33 in the treated group and 30 in the control group, who were treated respectively with HXC and domperidone for 4 weeks to observe the clinical effect and changes in electrogastrogram (EGG) before and after treatment.
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Three conserved serine residues (Ser193, Ser194, and Ser197) in transmembrane spanning region (TM) V of the D2 dopamine receptor have been mutated to alanine, individually and in combination, to explore their role in ligand binding and G protein coupling. The multiple Ser -->Ala mutations had no effect on the binding of most antagonists tested, including [3H]spiperone, suggesting that the multiple mutations did not affect the overall conformation of the receptor protein. Double or triple mutants containing an Ala197 mutation showed a decrease in affinity for domperidone, whereas Ala193 mutants showed an increased affinity for a substituted benzamide, remoxipride. However, dopamine showed large decreases in affinity (>20-fold) for each multiple mutant receptor containing the Ser193Ala mutation, and the high-affinity (coupled) state of the receptor (in the absence of GTP) could not be detected for any of the multiple mutants. A series of monohydroxylated phenylethylamines and aminotetralins was tested for their binding to the native and multiple mutant D2 dopamine receptors. The results obtained suggest that Ser193 interacts with the hydroxyl of S-5-hydroxy-2-dipropylaminotetralin (OH-DPAT) and Ser197 with the hydroxyl of R-5-OH-DPAT. We predict that Ser193 interacts with the hydroxyl of R-7-OH-DPAT and the 3-hydroxyl (m-hydroxyl) of dopamine. Therefore, the conserved serine residues in TMV of the D2 dopamine receptor are involved in hydrogen bonding interactions with selected antagonists and most agonists tested and also enable agonists to stabilise receptor-G protein coupling.
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Potentiometric sensors can be used to determine the amount of API dissolved in the dissolution medium in function of time by measuring directly in the dissolution vessel of a Paddle (USP type 2) and Basket (USP type 1) apparatus. The prototype potentiometric sensor instrumentation showed very promising results for a selection of APIs with different physico-chemical properties. The applicability, benefits and limitations of the prototype were explored. The applicability of the measurement technique strongly depends on the log(P) of the API. Here, it is shown that measurements can easily be performed for APIs with a log(P)>4. Electrode performance however decreases with decreasing logP of the APIs due to decreased drug selectivity in comparison to the excipients and ionic strength of the applied dissolution medium. The potentiometric sensors are shown to be insensitive towards undissolved particles and air bubbles as opposed to UV spectrometric measurement where these can lead to severe light scattering. For the tested APIs, the obtained dissolution profiles are very reproducible and show a low variation compared to the measurements using manual sampling and UV or HPLC analysis. The measurements demonstrate that potentiometric sensors are a very promising technology that can become a standard for in situ dissolution measurements.
There is currently no effective treatment for patients with nonulcer dyspepsia. Helicobacter pylori eradication has no beneficial effect on dyspeptic symptoms. Proton pump inhibitors are superior to placebo in the subset of patients with epigastric pain as the predominant symptom. H(2 )Receptor antagonists have no effect. Patients with dysmotility-like dyspepsia should be treated first with prokinetics. Unfortunately, cisapride no longer can be used to treat patients with functional dyspepsia because of reports of serious cardiovascular side effects and subsequent withdraw from the US market. Therefore, metoclopramide (or domperidone, if available) should be given. Treatment with motilides has no use in the relief of symptoms, even in patients with delayed gastric emptying. If the initial therapy has no effect after 4 weeks, switch treatment (eg, from proton pump inhibitor to metoclopramide or vice versa). If both of these pharmacologic therapies fail, consider treatment with an antidepressant (or with buspirone, an anxiolytic agent) or psychotherapy.
Drug-induced extrapyramidal symptoms (DIEPS) often substantially compromise quality of life (QOL) of patients receiving drugs with central antidopaminergic activities. A lack of comprehensive screening method based upon patients' subjective symptoms for detecting DIEPS appears to have prevented pharmacists from delivering satisfactory pharmaceutical care for these patients. Thus, we have attempted to develop a comprehensive questionnaire for screening patients having higher risks of developing DIEPS.
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Mothers of hospitalized premature infants who choose to provide breast milk are at increased risk of an inadequate breast milk supply. When nonpharmacologic interventions to increase milk supply fail, clinicians are faced with limited options. There is no current evidence to support the use of herbal galactogogues in this population and a black box warning for metoclopramide for potential serious side effects. Thus, domperidone was the only known, effective option for treatment of low milk supply in this population. With a thorough review of the literature on domperidone and coordination with the obstetrical, neonatal, lactation, and pharmacology teams, a domperidone treatment protocol for mothers of hospitalized premature infants with insufficient milk supply was developed at our institution and is presented in this article. A comprehensive understanding of domperidone for use as a galactogogue with a standard treatment protocol will facilitate safer prescribing practices and minimize potential adverse reactions in mothers and their hospitalized premature infants.
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The characteristics of warning symptoms preceding the migraine headache attack in 49 patients with complete migraine are described. These symptoms are divided into non-evolutive and evolutive warning symptoms, based on specific characteristics of each. Non-evolutive symptoms precede the attack by 8 to 48 h in 88% of our patients and have a constant and modest intensity. Evolutive warning symptoms appear within a few minutes up to 6 h before the attack. These symptoms become more and more pronounced towards the onset of the headache. There was no striking similarity between symptoms during the attack and the warning symptoms. In a number of patients with complete migraine, migraine attacks can be prevented by taking domperidone, a peripheral dopamine antagonist, at the time of the non-evolutive warning symptoms. These data suggest that the mechanism leading to a migraine attack can be operative 8-48 h before the headache begins and is possibly dopaminergically mediated.
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Previous studies from our laboratory have determined that inner medullary collecting duct (IMCD) cells express a novel DA2-like dopamine receptor (namely, DA2K) that is linked to prostaglandin E2 (PGE2) production. In the present study, we have further characterized the dopamine-stimulated PGE2 response. Dopamine stimulated PGE2 production in cultured IMCD cells dose dependently (concentration for half-maximal stimulation, 11.1 microM; maximal stimulation, 235.1% of basal), an effect that was blocked by the DA2 antagonists domperidone and (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)-methyl] benzamine. Inhibition of intracellular calcium release with 8-(diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (100 microM) blocked the dopamine response, whereas voltage-dependent calcium-channel blockers had no effect. Inhibition of phospholipase A2 (PLA2) activity with quinacrine (100 microM) completely blocked the dopamine-stimulated PGE2 production, whereas inhibition of polyphosphoinositol hydrolysis with neomycin (100 microM) or inhibition of protein kinase C with 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (10 microM) did not. Pertussis toxin (PT) treatment completely blocked the dopamine-stimulated PGE2 production but not the arachidonic acid-stimulated PGE2 production. These results suggest that dopamine, acting through the DA2K receptor, may be an important regulator of PGE2 production in IMCD cells. Furthermore, our results are most consistent with either a direct interaction of the DA2K receptor with PLA2 through a PT-sensitive G protein or an indirect interaction with PLA2 through mobilization of intracellular calcium.
The possibility to use the new ligand 3H-domperidone to identify some dopamine binding sites at the ultrastructural level was assessed in the neostriatum after in vivo administration and high-resolution radioautography. Since this ligand does not cross the blood-brain barrier, intracerebral injections were performed, which resulted in a gradient of diffusion of the tracer. According to increasing distances to the injection site, a quantitative study of the radioautographic reaction was realized. An intense and diffuse reaction took place in the vicinity of the injection site in control rats. On the contrary, numerous accumulations of silver grains were observed in the peripheral zone. The statistical analysis of the distribution of the clusters showed that they were more numerous over the contacts between nerve terminals and dendritic spines than expected from a distribution at random; moreover half of these labelled contacts were differentiated in synapses of the asymmetric type. When the animals were pretreated with haloperidol in order to block the dopaminergic binding sites, we found a decrease in the total number of the number of silver grains. A decrease in the number of clusters of silver grains was noted over nerve terminals and synaptic contacts in both peripheral zones while the nonspecific labelling was increased over other structures. We conclude to the possibility of the detection of the dopaminergic binding sites by electron microscopic radioautography. Moreover we confirm the existence of dopaminergic synapses in the neostriatum with this new technique.
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Forty-six mothers who had delivered infants at <31 weeks' gestation, who experienced lactation failure, were randomly assigned to receive domperidone or placebo for 14 days. Protein, energy, fat, carbohydrate, sodium, calcium, and phosphate levels in breast milk were measured on days 0, 4, 7, and 14, serum prolactin levels were measured on days 0, 4, and 14, and total milk volume was recorded daily. Mean within-subject changes in nutrients and milk volumes were examined.
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Two simple, accurate and precise spectrophotometric methods have been developed for simultaneous determination of lansoprazole and domperidone in pharmaceutical dosage form. Method A involves formation of Q-absorbance equation at 256.0 nm (isoabsorptive point) and at 294.2 nm while method B is two wavelength method where 277.6 nm, 302.1 nm were selected as lambda(1) and lambda(2) for determination of lansoprazole and 231.3 nm, 292.0 nm were selected as lambda(1) and lambda(2) for determination of domperidone. Both the methods were validated statistically and recovery studies were carried out. The Beer's law limits for each drug individually and in mixture was within the concentration range of 5-50 mug/ml. Linearity of lansoprazole and domperidone were in the range of 24-36 mug/ml and 8-12 mug/ml, respectively. The proposed methods have been applied successfully to the analysis of the cited drugs either in pure form or in pharmaceutical formulations with good accuracy and precision. The method herein described can be employed for quality control and routine analysis of drugs in pharmaceutical formulations.
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This study aimed to examine factors associated with the use of domperidone as a galactogogue at the Women's and Children's Hospital (WCH), Adelaide.
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The pathophysiology, diagnosis, and treatment of diabetic gastroparesis are reviewed, and the mechanisms of action, pharmacokinetics, clinical efficacy, adverse effects, and dosage of metoclopramide, domperidone, and cisapride are described. Diabetic gastroparesis is a state of delayed gastric emptying that reportedly affects 20-30% of diabetic patients. Symptoms include nausea, early satiety, postprandial bloating and fullness, and vomiting. Diabetic gastroparesis has been managed most successfully with drugs that stimulate gastric emptying. Of the three agents studied--metoclopramide, domperidone, and cisapride--only metoclopramide is commercially available in the United States. The clinical efficacy of metoclopramide, domperidone, and cisapride has been well documented in several placebo-controlled trials. Metoclopramide effectively decreases mean gastric emptying time, although tolerance to this stimulation of gastric emptying may develop with long-term therapy. However, symptomatic relief persists with long-term therapy because of metoclopramide's antiemetic properties. Domperidone, which has also been shown to stimulate gastric motility and to possess antiemetic properties, improves symptoms in patients suffering from diabetic gastroparesis. Cisapride appears to have continued beneficial effects on gastric motility with long-term therapy. All three agents have favorable adverse-effect profiles. Although metoclopramide is currently the first-line agent for the management of gastroparesis, domperidone and cisapride both possess properties that may make them useful alternatives in patients who are unresponsive to or cannot tolerate metoclopramide therapy.
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Some preterm infants in general good health continue to present recurrent apnoeas, bradycardias and desaturations (ABD) despite usual treatments. These events may lead to transitory brain hypoxia and to further neurological injury. The purpose of this study has been to evaluate the role of laryngeal oedema in this symptomatology and to assess corticoid treatment.