Publications by authors named "Rosa Mostardini"

15 Publications

  • Page 1 of 1

A case of Friedreich ataxia in an adolescent with 16p11.2 microdeletion syndrome.

Neurol Sci 2020 03 2;41(3):721-722. Epub 2019 Oct 2.

Dipartimento di Medicina Molecolare e dello Sviluppo, Universita' degli Studi di Siena, viale Bracci, 53100, Siena, Italy.

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http://dx.doi.org/10.1007/s10072-019-04075-zDOI Listing
March 2020

Epilepsy in Mowat-Wilson syndrome: delineation of the electroclinical phenotype.

Am J Med Genet A 2013 Feb 15;161A(2):273-84. Epub 2013 Jan 15.

Child Neurology and Psychiatry Unit, S Orsola Malpighi Hospital, University of Bologna, Bologna, Italy.

Mowat-Wilson syndrome (MWS) is a genetic disease caused by heterozygous mutations or deletions of the ZEB2 gene and is characterized by distinctive facial features, epilepsy, moderate to severe intellectual disability, corpus callosum abnormalities and other congenital malformations. Epilepsy is considered a main manifestation of the syndrome, with a prevalence of about 70-75%. In order to delineate the electroclinical phenotype of epilepsy in MWS, we investigated epilepsy onset and evolution, including seizure types, EEG features, and response to anti-epileptic therapies in 22 patients with genetically confirmed MWS. Onset of seizures occurred at a median age of 14.5 months (range: 1-108 months). The main seizure types were focal and atypical absence seizures. In all patients the first seizure was a focal seizure, often precipitated by fever. The semiology was variable, including hypomotor, versive, or focal clonic manifestations; frequency ranged from daily to sporadic. Focal seizures were more frequent during drowsiness and sleep. In 13 patients, atypical absence seizures appeared later in the course of the disease, usually after the age of 4 years. Epilepsy was usually quite difficult to treat: seizure freedom was achieved in nine out of the 20 treated patients. At epilepsy onset, the EEGs were normal or showed only mild slowing of background activity. During follow-up, irregular, diffuse frontally dominant and occasionally asymmetric spike and waves discharges were seen in most patients. Sleep markedly activated these abnormalities, resulting in continuous or near-to-continuous spike and wave activity during slow wave sleep. Slowing of background activity and poverty of physiological sleep features were seen in most patients. Our data suggest that a distinct electroclinical phenotype, characterized by focal and atypical absence seizures, often preceded by febrile seizures, and age-dependent EEG changes, can be recognized in most patients with MWS.
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http://dx.doi.org/10.1002/ajmg.a.35717DOI Listing
February 2013

Epilepsy, speech delay, and mental retardation in facioscapulohumeral muscular dystrophy.

Eur J Paediatr Neurol 2011 Sep 16;15(5):456-60. Epub 2011 Jul 16.

Department of Pediatrics, Gynecology, Obstetrics, and Reproductive Medicine, Pediatric Neurology Section, University of Siena, Italy.

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies which is related to the deletion of tandem repeats on chromosome 4q35. Extramuscular features such as hearing loss, retinopathy, mental retardation, and epilepsy, may be observed in patients carrying large 4q35 deletions resulting in fragment sizes less than 12 kilobases (kb) (normal >35 kb). We report on a family affected by FSHD carrying a small 4q35 deletion and residual fragments length of 17 kb, presenting with epilepsy (three patients), speech delay (two), and mental retardation (one). In all patients semeiology of seizures and interictal EEG anomalies were congruent with a localization-related epilepsy possibly involving the temporal lobe. In conclusion, we provide further evidences that extramuscular findings such as epilepsy, speech delay, and mental retardation may occur in those patients carrying smaller 4q35 deletions, suggesting that a close correlation between 4q35 fragment size and clinical severity in FSHD is therefore not constant. Moreover, a review of the literature and our observations seem to suggest that focal epilepsies, likely related to the temporal lobe in the present family, represent the main type of epilepsy occurring in children with FSHD.
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http://dx.doi.org/10.1016/j.ejpn.2011.04.003DOI Listing
September 2011

Circulating levels of allopregnanolone, a neuroactive steroid, and leptin during treatment with valproic acid in children with epilepsy.

Neuroendocrinology 2011 27;93(3):159-64. Epub 2010 Oct 27.

Department of Pediatrics, Obstetrics, Gynecology and Reproductive Medicine, Pediatric Neurology Section, University of Siena, Siena, Italy.

Weight gain is a well-known unwanted effect of valproic acid (VPA) therapy. Studies on VPA-associated changes of homeostatic hormones remain limited and controversial. Allopregnanolone (AP) is a circulating neuroactive steroid involved in modulation of behavioral activities whose serum levels are increased in obese children. The aim of the present study was to determine whether VPA therapy affects leptin and AP circulating levels in prepubertal girls with epilepsy. One-hundred and one patients were divided into four groups: epileptic patients with VPA-associated obesity (n = 21); lean epileptic patients under VPA therapy (n = 35); healthy obese children (n = 23), and healthy lean children (n = 22). Patients with VPA-associated obesity had significantly enhanced blood concentrations of AP (p = 0.001) and leptin (p = 0.007) than lean subjects. There were no differences in leptin and AP plasma levels between patients with VPA-associated obesity and obese controls (p = 0.45 and p = 0.10, respectively), as there were no differences between lean patients under VPA therapy and lean healthy controls (p = 0.06). In patients under VPA therapy, both plasma leptin and AP levels were significantly correlated with BMI (r = 0.074, p = 0.02, and r = 0.084, p = 0.01, respectively). Plasma leptin concentrations were not correlated with AP levels (r = 0.023, p = 0.13). In conclusion, a correlation between obesity and neuroactive steroids was shown. It remains to be established whether the increased circulating level of AP is a secondary effect of anxiolytic-sedative processes occurring in subjects with obesity-related emotional and behavioral anomalies, or plays a central role in determining abnormal eating behaviors.
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http://dx.doi.org/10.1159/000321664DOI Listing
July 2011

Body mass index and serum lipid changes during treatment with valproic acid in children with epilepsy.

Ann Pharmacother 2009 Jan 9;43(1):45-50. Epub 2008 Dec 9.

Pediatric Neurology Section, Department of Pediatrics, Obstetrics, Gynecology and Reproductive Medicine, University of Siena, Siena, Italy.

Background: Valproic acid is the drug of choice for a wide variety of epileptic seizures and syndromes because of its broad spectrum of activity and because, in most patients, it is well tolerated. Although weight gain is a well-known adverse effect of valproic acid therapy, only a few studies have addressed weight gain associated with it in children aged 2-8 years.

Objective: To evaluate valproic acid-associated changes in the body mass index (BMI) z-scores and to assess changes in serum triglyceride, cholesterol, and fasting glucose levels in young children receiving valproic acid treatment.

Methods: Eighty-seven patients (39 females, 48 males) receiving valproic acid therapy for at least 3 months were included in the retrospective longitudinal study. Mean +/- SD age at initiation of therapy was 4.8 +/- 0.8 years. Changes in BMI z-scores as well as serum triglyceride, total cholesterol, and fasting glucose levels were evaluated as continuous variables and analyzed by longitudinal methods for all patients.

Results: The average change from baseline in BMI z-scores was 0.80 (p = 0.001) at 3.1 years of follow-up. No significant change in triglyceride, cholesterol, and serum fasting glucose levels was observed over the same period. The percentage of overweight children at baseline was 6.9% and rose to 16% by the final visit (p = 0.081).

Conclusions: Valproic acid-associated weight gain may occur in young children. However, only 16% of patients were categorized as overweight at the end of the study; this percentage overlaps the percentage of overweight healthy young Italian children. The BMI z-scores significantly increased during the first 16 months of therapy, then appeared to level off. These observations may influence clinical practice and decision-making regarding suspending the drug due to weight gain in children in whom seizure control has been achieved.
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http://dx.doi.org/10.1345/aph.1L414DOI Listing
January 2009

Private inherited microdeletion/microduplications: implications in clinical practice.

Eur J Med Genet 2008 Sep-Oct;51(5):409-16. Epub 2008 Jul 9.

Medical Genetics, Molecular Biology Department, University of Siena, Viale Bracci 2, 53100 Siena, Italy.

The introduction of array-CGH analysis is allowing the identification of novel genomic disorders. However, this new high-resolution technique is also opening novel diagnostic challenges when inherited private CNVs of unclear clinical significance are found. Oligo array-CGH analysis of 84 patients with mild to severe mental retardation associated with multiple congenital anomalies revealed 10 private CNVs inherited from a healthy parent. Three were deletions (7q31, 14q21.1, Xq25) and seven duplications (12p11.22, 12q21.31, 13q31.1, 17q12, Xp22.31, Xq28) ranging between 0.1 and 3.8Mb. Six rearrangements were not polymorphic. Four overlapped polymorphic regions to the extent of 10-61%. In one case the size was different between the proband and the healthy relative. Three small rearrangements were gene deserts. The remaining seven had a mean gene content of five (ranging from 1 to 18). None of the rearranged genes is known to be imprinted. Three disease-genes were found in three different cases: KAL1 in dupXp22.31, STS in another dupXp22.31 and TCF2 in dup17q12. The patient carrying the last duplication presents sex reversal, Peters' anomaly and renal cysts and the duplication is located 4Mb away from the HSD17B1 gene, coding a key enzyme of testosterone biosynthesis. Considering the overlap with polymorphic regions, size-identity within the family, gene content, kind of rearrangement and size of rearrangement we suggest that at least in five cases the relationship to the phenotype has not to be excluded. We recommend to maintain caution when asserting that chromosomal abnormalities inherited from a healthy parent are benign. A more complex mechanism may in fact be involved, such as a concurrent variation in the other allele or in another chromosome that influences the phenotype.
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http://dx.doi.org/10.1016/j.ejmg.2008.06.003DOI Listing
November 2008

Topiramate effects on plasma serotonin levels in children with epilepsy.

Epilepsy Res 2008 Oct 7;81(2-3):148-54. Epub 2008 Jul 7.

Department of Pediatrics, Pediatric Neurology Section, University of Siena, Italy.

Topiramate (TPM) is a new, effective and safe antiepileptic drug. TPM is also effective in treating a wide spectrum of conditions such as eating disorders and related anomalies, bulimia nervosa and other conditions in which serotonin (5-hydroxytryptamine, 5-HT) is involved pathogenetically. Plasma serotonin mainly derives from blood platelets, which represent a valid model of serotoninergic neurons. We measured plasma 5-HT levels in 12 children affected by epilepsy who underwent TPM therapy. Inclusion criteria were (i) age range 2-12 years, (ii) weight greater than 12 kg, (iii) no more than one antiepileptic drug used when TPM therapy was instituted, and (iv) a minimum study period of 3 months. After a mean period of 3 months of TPM treatment, a significant increase in mean plasma serotonin levels was observed with respect to the basal levels and those of a control group. There were no significant correlations between the changes in serotonin concentrations and the antiepileptic efficacy or doses of TPM used. TPM may influence serotonin metabolism in children affected by epilepsy. Further studies are needed to establish whether these serotonin plasma changes represent an epiphenomenon or indicate direct effects of TPM on the serotoninergic system.
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http://dx.doi.org/10.1016/j.eplepsyres.2008.05.007DOI Listing
October 2008

A comparative study of hydrocortisone versus deflazacort in drug-resistant epilepsy of childhood.

Epilepsy Res 2008 Sep 3;81(1):80-5. Epub 2008 Jun 3.

Department of Pediatrics, Pediatric Neurology Section, University of Siena, Viale M. Bracci, Le Scotte, Siena, Italy.

Steroids are commonly used for the treatment of intractable epilepsy. Deflazacort has shown similar effects to prednisone, but with a less worrying adverse-effect profile. In this study, we first compared the efficacy, safety, and seizure relapse rate of deflazacort versus hydrocortisone in children affected by drug-resistant epilepsies. This was an open, non-blinded, randomized clinical study of 35 children affected by drug-resistant epilepsies. The study lasted 12 months. Group 1 (16 patients) received hydrocortisone for 6 months; group 2 (19 patients) was treated with deflazacort for the entire study period. Drug efficacy and tolerability were evaluated after 6 months of therapy. Seizure relapse rates were evaluated 12 months after the start of the study. After 6 months of therapy, hydrocortisone was effective in 44% of patients (responders, with a decrease in seizure frequency of >50%). Deflazacort was effective in 47% of patients (P=0.9). Adverse events occurred in 37% of patients using hydrocortisone and in none of those using deflazacort (P=0.002). At the end of the study, seizure relapse rate resulted significantly higher in group 1 than in group 2 (P=0.04). Hydrocortisone may be useful in the treatment of severely drug-resistant childhood epilepsies. However, its effects may be transient. Deflazacort should be considered in the therapeutic armamentarium for epileptic encephalopathies. The drug is as effective as hydrocortisone and may be used in therapy for a long period, with a less worrying adverse-effect profile.
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http://dx.doi.org/10.1016/j.eplepsyres.2008.04.016DOI Listing
September 2008

Post-ictal circulating levels of allopregnanolone in children with partial or generalized seizures.

Epilepsy Res 2005 Feb;63(2-3):97-102

Department of Pediatrics, Obstetrics, and Reproductive Medicine, University of Siena, Viale M. Bracci, Le Scotte, 53100 Siena, Italy.

Introduction: Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one) is a neurosteroid with a potent modulating activity on the gamma-aminobutyric acid (GABA)(a) receptor complex. It plays a key role in the epileptogenesis of partial seizures. Serum allopregnanolone concentrations significantly increase in the postcritical phase. In the present study we investigated the post-ictal serum allopregnanolone levels in children with partial seizures and generalized seizures, respectively.

Patients And Methods: Three groups of subjects were included in the study. Group 1 consisted of 18 children affected by complex partial seizures. Group 2 consisted of 11 children presenting with generalized epilepsy. Group 3 consisted of 20 healthy age-matched subjects. Serum allopregnanolone levels were assayed in the inter-ictal phase and within 30 min after an epileptic event.

Results: The data we obtained suggest that circulating allopregnanolone level significantly increases in the post-ictal phase. However, we found no significant differences in the post-ictal serum allopregnanolone concentrations between patients with partial seizures and those with generalized seizures.

Conclusions: Further studies are needed to establish if allopregnanolone is a reliable circulating marker of epileptic seizures. However, our observations seem to indicate that post-ictal circulating allopregnanolone level is not useful in differentiating focal and generalized epilepsy events.
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http://dx.doi.org/10.1016/j.eplepsyres.2004.12.002DOI Listing
February 2005

Epilepsy and electroencephalographic findings in pericentric inversion of chromosome 12.

J Child Neurol 2004 Aug;19(8):604-8

Department of Pediatrics, University of Siena, Siena, Italy.

Epilepsy, together with mental retardation, represents a common manifestation of chromosomal aberrations. Specific electroencephalographic (EEG) and epileptic patterns have been described in several chromosomal disorders, such as Angelman's syndrome, Miller-Dieker syndrome, Wolf-Hirschhorn syndrome, and ring 20 syndrome. A peculiar electroclinical pattern has also been identified in trisomy 12p syndrome. We report three patients with a pericentric inversion of chromosome 12, with breakpoints localized to p11-q13 and affected by epilepsy or EEG anomalies. Two suffered from epilepsy, which, in the clinical course, was mainly characterized by complex partial seizures with a semiology related to the temporal lobe. In one patient, myoclonic absences, head drop, and massive jerky attacks were also present. In both patients, generalized 3 Hz bursts were registered, together with multifocal and focal paroxysmal activity, which were most prominent in the temporoparietal and temporal areas, respectively. In the other patient, who had no epilepsy, EEG showed bioccipital paroxysmal activity. In all patients, the clinical picture was characterized by the presence of moderate mental retardation and behavioral disorders. The incidence of epilepsy or EEG anomalies among patients with a pericentric inversion of chromosome 12 remains to be ascertained. However, the present study confirms that chromosome 12 anomalies can be associated with epilepsy. Although myoclonic absence-like episodes can occasionally be part of the epileptic phenotype, the electroclinical pattern in pericentric inversion of chromosome 12 seems to be more polymorphic when compared with that observed in trisomy 12p syndrome.
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http://dx.doi.org/10.1177/088307380401900807DOI Listing
August 2004

Electroencephalographic and epileptic patterns in X chromosome anomalies.

J Clin Neurophysiol 2004 Jul-Aug;21(4):249-53

Department of Pediatrics, University of Siena, Siena, Italy.

Although epilepsy and mental retardation are commonly observed in individuals with chromosomal aberrations, the identification of EEG/epileptic profiles in those with specific chromosome anomalies remains difficult. A few syndromes seem to show peculiar clinical and EEG associations. The authors report an electroclinical investigation on a group of patients carrying X chromosome anomalies: 16 patients with Turner's syndrome, 17 with Klinefelter's syndrome, 1 with an X-autosomal rearrangement, 2 with Xq isochromosome [Xq(i)], and 7 with triple X syndrome. Epilepsy and/or EEG anomalies were found in three of the patients with Klinefelter's syndrome, in one patient with an X-autosomal rearrangement, and in five of those with triple X syndrome. No epilepsy or EEG anomalies were detected in the other patients. Epilepsy may be associated with Klinefelter's syndrome. In addition, the authors found that an electroclinical pattern, represented by paroxysmal activity in the posterior regions (temporo-parieto-occipital areas) with complex partial seizures and easily controlled by antiepileptic drugs, may be present in patients with triple X syndrome. In contrast, gross X-autosomal rearrangements are associated with polymorphic EEG/epileptic findings. Although further studies are needed to validate these observations, they clearly confirm the strict relationship between X chromosome anomalies and epilepsy.
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http://dx.doi.org/10.1097/00004691-200407000-00003DOI Listing
December 2004

Medial temporal lobe dysgenesis in Muenke syndrome and hypochondroplasia.

Am J Med Genet A 2003 Jul;120A(1):88-91

Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Viale M. Bracci-Le Scotte, 53100 Siena, Italy.

Hypochondroplasia (HCH) and Muenke syndrome (MS) are caused by mutations on FGFR3 gene. FGFR3 is known to play a role in controlling nervous system development. We describe the clinical and neuroradiological findings of the first two patients, to our knowledge, affected by HCH and MS, respectively, in whom bilateral dysgenesis of the medial temporal lobe structures has been observed. In both patients diagnosis was confirmed by molecular analysis. They were mentally normal and showed similarities in early-onset temporal lobe-related seizures. In both patients EEG recorded bilateral temporal region discharges. MRI detected temporal lobe anomalies with inadequate differentiation between white and gray matter, defective gyri, and abnormally shaped hippocampus.
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http://dx.doi.org/10.1002/ajmg.a.10171DOI Listing
July 2003

Inter-ictal and post-ictal circulating levels of allopregnanolone, an anticonvulsant metabolite of progesterone, in epileptic children.

Epilepsy Res 2003 Apr;54(1):29-34

Department of Pediatrics, Obstetrics, and Reproductive Medicine, University of Siena, Viale M. Bracci, Le Scotte, Siena 53100, Italy.

Allopregnanolone belongs to a group of neuroactive steroid hormones, or neurosteroids, synthesized and acting within the brain and is as a potent endogenous positive modulator of GABA(A) receptor complex. Administration of allopregnanolone protects rats against pentylentetrazol, bicuculline, kainic acid, and picrotoxin-induced seizures. We investigated serum allopregnanolone levels in children with active epilepsy at pubertal Tanner's stage I (n=52). Blood specimens were collected at least 12 h after a seizure (inter-ictal). In a subgroup of patients (n=11), specimens were also collected within 30 min from a seizure attack (post-ictal). Healthy age-matched children (n=18) served as controls. Serum allopregnanolone was measured by radioimmunoassay using a polyclonal antiserum. The inter-ictal serum allopregnanolone levels in the epileptic children were not statistically different from those detected in the control group, whereas post-ictal levels were significantly higher than the inter-ictal ones (P=0.0001). In this subgroup of patients allopregnanolone levels decreased to the basal values during the following 12 h. Serum allopregnanolone levels may therefore reflect changes in neuronal excitability, and allopregnanolone appears to be a reliable circulating marker of epileptic seizures. It is possible that increased post-ictal serum levels of allopregnanolone may play a role in modulating neuronal excitability and may represent an endogenous mechanism of seizure control.
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http://dx.doi.org/10.1016/s0920-1211(03)00042-1DOI Listing
April 2003

Ethylmalonic encephalopathy: further clinical and neuroradiological characterization.

J Neurol 2002 Oct;249(10):1446-50

Department of Pediatrics, Obstetrics, and Reproductive Medicine, University of Siena, Viale M. Bracci--Le scotte, 53100 Siena, Italy.

Ethylmalonic encephalopathy (EE) is a rare metabolic disorder with an autosomal recessive mode of inheritance that is clinically characterized by neuromotor delay, hyperlactic acidemia, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhea. Increased urinary levels of ethylmalonic acid and methylsuccinic acid are the main biochemical features of the disorder. We report on two patients affected by EE who showed different clinical and neuroradiological patterns. Patient 1 presented with a chronic clinical course characterized by very slow neuromotor deterioration, ataxia, and dysarthria. In contrast, patient 2 had an acute neonatal onset with severe neuromotor retardation, severe generalized hypotonia, and intractable seizures. Neuroradiological follow-up of patient 1 detected a diffuse hyperintensity on the T2 images at the basal ganglia which remained stable during a period of four years. Patient 2, in contrast, showed a rapid process of cerebral, and in part, cerebellar atrophy. On the basis of our observations, we reviewed the data published in the literature and tried to delineate the natural history of EE, which appears to be characterized by a wide spectrum of severity in the clinical course. No reports on neuroradiological follow-up of EE patients are available in the literature with which to compare our data. Finally, both patients showed a muscle COX deficiency. The pathogenetic implications of such a biochemical finding will be also discussed.
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http://dx.doi.org/10.1007/s00415-002-0880-4DOI Listing
October 2002

Recurrent torticollis caused by dissecting vertebral artery aneurysm in a pediatric patient: results of endovascular treatment by use of coil embolization: case report.

Neurosurgery 2002 Jan;50(1):204-7; discussion 207-8

Department of Pediatrics, University of Siena, Siena, Italy.

Objective And Importance: Torticollis is a symptom that can be related to different pathological mechanisms ranging from simple to life-threatening conditions. We report a child with recurrent torticollis caused by an intracranial dissecting vertebral artery aneurysm. This is a very rare condition in childhood, and it was resolved successfully with endovascular treatment.

Clinical Presentation: The patient was a 10-year-old boy with a 4-year history of left recurrent torticollis, followed by hemiparesis, dysarthria, dysmetria, and tremor. Brain magnetic resonance imaging and digital angiography detected a dissecting aneurysm involving the fourth segment of the left vertebral artery.

Intervention: The patient underwent endovascular treatment. Coil embolization, followed by histoacryl injection into the lesion, provided complete obliteration of the aneurysmal sac.

Conclusion: The patient's postoperative course was characterized by a dramatic disappearance of symptoms and signs within a few hours of the intervention. No relapses of symptoms occurred during a follow-up period of 18 months. This is the first report of a child in whom recurrent torticollis was related to a dissecting vertebral artery aneurysm. Although long-term results of vertebral artery coil embolization remain to be elucidated, the method seems reliable and effective in treatment of these vascular lesions in pediatric patients.
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http://dx.doi.org/10.1097/00006123-200201000-00031DOI Listing
January 2002