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BACKGROUND: Growth hormone (GH) treatment is effective in improving adult height (AH) in short children born SGA. However, there is a wide variation in height gain, even after adjustment for predictive variables. It is therefore important to investigate new factors which can influence the response to GH. OBJECTIVE: To investigate the efficacy of GH treatment (1 mg/m(2/) day) in short SGA children on AH. To assess the relation between spontaneous catch-up growth after birth and growth during puberty on the total height gain SDS to AH. PATIENTS: Longitudinal GH trial in 170 children. RESULTS: Median age at start of GH was 7·1 years and height -3·0 SDS. AH was -1·8 SDS (TH-corrected AH -1·1 SDS) in boys and -1·9 SDS (TH-corrected AH -1·3 SDS) in girls. Spontaneous catch-up growth after birth was ≥0·5 SDS in 42% of children. In contrast to expectation, spontaneous catch-up growth was negatively correlated with total height gain SDS during GH (P = 0·009). During puberty, height SDS declined (-0·4 SDS in boys and -0·5 SDS in girls) resulting in a lower total height gain SDS than expected. Pubertal height gain was 25·5 cm in boys and 15·3 cm in girls, significantly lower compared to AGA children (P < 0·001). At onset of puberty, BA for boys and girls was moderately advanced (P = 0·02 and P < 0·001, respectively). Growth velocity was comparable to AGA children during the first two years of puberty, but thereafter significantly lower until reaching AH (P < 0·001). CONCLUSION: In contrast to our hypothesis, children with greater spontaneous catch-up growth after birth show a lower total height gain SDS during GH. Height SDS declines from mid-puberty, due to a marked early deceleration of growth velocity.
Assuntos
Estatura/efeitos dos fármacos , Desenvolvimento Humano , Hormônio do Crescimento Humano , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Substâncias de Crescimento/administração & dosagem , Substâncias de Crescimento/efeitos adversos , Desenvolvimento Humano/efeitos dos fármacos , Desenvolvimento Humano/fisiologia , Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/efeitos adversos , Humanos , Recém-Nascido , Estudos Longitudinais , Masculino , Países BaixosRESUMO
The gradual shifting of preferred neural spiking relative to local field potentials (LFPs), known as phase precession, plays a prominent role in neural coding. Correlations between the phase precession and behavior have been observed throughout various brain regions. As such, phase precession is suggested to be a global neural mechanism that promotes local neuroplasticity. However, causal evidence and neuroplastic mechanisms of phase precession are lacking so far. Here we show a causal link between LFP dynamics and phase precession. In three experiments, we modulated LFPs in humans, a non-human primate, and computational models using alternating current stimulation. We show that continuous stimulation of motor cortex oscillations in humans lead to a gradual phase shift of maximal corticospinal excitability by ~90°. Further, exogenous alternating current stimulation induced phase precession in a subset of entrained neurons (~30%) in the non-human primate. Multiscale modeling of realistic neural circuits suggests that alternating current stimulation-induced phase precession is driven by NMDA-mediated synaptic plasticity. Altogether, the three experiments provide mechanistic and causal evidence for phase precession as a global neocortical process. Alternating current-induced phase precession and consequently synaptic plasticity is crucial for the development of novel therapeutic neuromodulation methods.
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BACKGROUND: Congenital gastrointestinal malformation (CGIM) require neonatal surgical treatment and may lead to disease-specific sequelae, which have a potential psychological impact on parents. The aim of this study is to assess distress and symptoms of post-traumatic stress disorder (PTSD) in parents of patients with CGIM. In this cross-sectional study, seventy-nine parents (47 mothers and 32 fathers) of 53 patients with CGIM completed the Distress Thermometer for Parents (DT-P) and the Self Rating Scale for Posttraumatic Stress Disorders (SRS-PTSD) as part of the multidisciplinary follow-up of their children (aged 5-35 months). Group differences were tested between parents and representative Dutch reference groups with regard to rates of (clinical) distress and PTSD, and severity of overall distress and PTSD, for mothers and fathers separately. Mixed model regression models were used to study factors associated with the risk of (clinical) distress, PTSD and with severity of symptoms of PTSD (intrusion, avoidance and hyperarousal). RESULTS: Prevalence of clinical distress was comparable to reference groups for mothers (46%) and fathers (34%). There was no difference in severity of overall distress between both mothers as well as fathers and reference groups. Prevalence of PTSD was significantly higher in mothers (23%) compared to the reference group (5.3%) (OR = 5.51, p < 0.001), not in fathers (6.3% vs 2.2.%). Symptoms of intrusion were commonly reported by all the parents (75%). Longer total length of child's hospital stay was associated with more severe symptoms of intrusion, avoidance and hyperarousal. Child's length of follow-up was negatively associated with severity of intrusion. CONCLUSIONS: Having a child with CGIM has a huge impact on parents, demonstrated by a higher prevalence of PTSD in mothers, but not fathers, compared to parents in the general population. Monitoring of symptoms of PTSD of parents in follow-up is necessary.
Assuntos
Transtornos de Estresse Pós-Traumáticos , Criança , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Mães/psicologia , Pais/psicologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologiaRESUMO
OBJECTIVE: The aim of this prospective study was to assess the prognostic value of electroencephalography in infants born with spina bifida.31 infants with spina bifida born between 2002 and 2007 at the Radboud Nijmegen University Medical Centre were evaluated and followed for 2½ years. Electroencephalography (EEG) was performed during the first 8 weeks after birth. RESULTS: EEG recordings were all within normal limits and showed no abnormalities. 3 of the 31 children showed mild mental disability and major physical disabilities at the age of 30 months. CONCLUSION: Single Infantile EEG recordings are of limited prognostic value for infants born with spina bifida. Serial EEG recordings in combination with other clinical or neurophysiological investigations might ameliorate the contributing predictive value of neonatal EEG.
Assuntos
Ondas Encefálicas/fisiologia , Deficiências do Desenvolvimento/fisiopatologia , Eletroencefalografia , Disrafismo Espinal/fisiopatologia , Progressão da Doença , Epilepsia/etiologia , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Estudos Retrospectivos , Disrafismo Espinal/diagnósticoRESUMO
OBJECTIVE: The aim of this study was to describe insulin resistance and the metabolic syndrome in obese children and adolescents. SUBJECTS: The cohort consisted of 518 patients, 250 boys, 268 girls, age +/- sd: 11.8 +/- 3.2 years, BMIsds +/- sd: 2.94 +/- 0.5. A standard OGTT was performed. RESULTS: Impaired glucose tolerance was found in 9.4% of the boys and 5.5% of the girls. Impaired fasting glucose was found in 12.4% of the boys and 11.6% of the girls. The metabolic syndrome was present in 13.9% of children of 10 years or older. The proportion in which the metabolic syndrome was diagnosed was essentially not altered when pubertal groups were used instead of age groups. CONCLUSION: Both impaired fasting glucose and impaired glucose tolerance as well as the metabolic syndrome are highly prevalent among obese children and adolescents.
Assuntos
Resistência à Insulina , Síndrome Metabólica/etiologia , Obesidade/complicações , Adolescente , Fatores Etários , Criança , Jejum/metabolismo , Feminino , Intolerância à Glucose , Humanos , Masculino , Encaminhamento e ConsultaRESUMO
Behavioral treatment of drooling is advocated widely, but evidence of its effectiveness is lacking. In a center-based case-series study, 10 participants with severe drooling were taught self-management skills to reduce drooling. Following treatment, all participants remained dry for intervals of 30-60 min, while being engaged in daily activities. Generalization to the classroom occurred in each participant. For three participants, maintenance of treatment effect was established at 6 and 24 weeks. Seven participants failed to maintain self-management skills at follow-up. Although the self-management procedure showed promising results, further adaptations are required to improve efficacy, generalization, and maintenance.
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Terapia Comportamental/métodos , Autocuidado/métodos , Sialorreia/terapia , Adolescente , Criança , Feminino , Seguimentos , Humanos , Masculino , Tempo de Reação , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Fetal growth retardation is associated with decreased postnatal growth, resulting in a lower adult height. In addition, a low birth weight is associated with an increased risk of developing diseases during adulthood, such as insulin resistance, type 2 diabetes mellitus, hypertension, dyslipidemia, and cardiovascular diseases. Children with persistent postnatal growth retardation, i.e., incomplete catch-up growth, can be treated with human GH. The GH/IGF-I axis is involved in the regulation of carbohydrate and lipid metabolism. The question of whether treatment with GH in children born small for gestational age (SGA) has long-term implications with respect to glucose/insulin and lipid metabolism has not been answered yet. In this article, the available data are reviewed.
Assuntos
Hormônio do Crescimento/uso terapêutico , Recém-Nascido Pequeno para a Idade Gestacional/crescimento & desenvolvimento , Recém-Nascido Pequeno para a Idade Gestacional/metabolismo , Estatura , Glucose/metabolismo , Transtornos do Crescimento/tratamento farmacológico , Humanos , Recém-Nascido , Insulina/metabolismo , Metabolismo dos LipídeosRESUMO
Spina bifida is a multifaceted neurological condition with complex neuropsychological sequelae. The cognitive outcome in spina bifida has frequently been attributed to the severity of the hydrocephalus. However, because of complex neuropathology, the influence of hydrocephalus alone does not sufficiently explain the deficits in the cognitive profile in spina bifida. To date, little is known of the role of Arnold-Chiari-II malformation (ACM) in the cognitive profile of these patients. Aim of the current study is to delineate the specific contribution of the ACM in spina bifida by comparing children with ACM and those without ACM. 46 children between 6 and 15 years of age underwent a neuropsychological assessment covering intelligence and a wide range of cognitive functions, such as visuo-motor processing, attention, memory, word fluency and speed of information processing. Comparisons were made between patients with ACM (ACM+) and those without ACM (ACM-); all children with ACM+ also had hydrocephalus. Confounding effects of global cognitive impairment were excluded, such that groups were matched on verbal IQ. Because of complex neuropathology, which is inherent to spina bifida, the method applied was based on a comparison of cognitive profiles of the study group with profiles of patients with cerebellar damage and hydrocephalus found in the literature. Impaired visual analysis and synthesis, verbal memory, and verbal fluency, even after correction for global cognitive impairment, were observed in children with ACM. The hypothesis that in addition to impairment in visual analysis and synthesis, which are related to both hydrocephalus and ACM, specific deficiencies in verbal memory and fluency may be attributed to ACM is supported.
Assuntos
Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/etiologia , Transtornos Cognitivos/etiologia , Disrafismo Espinal/complicações , Adolescente , Criança , Feminino , Humanos , Hidrocefalia/complicações , Hidrocefalia/etiologia , Masculino , Transtornos da Memória/etiologia , Testes Neuropsicológicos , Percepção VisualRESUMO
Is 'hopeless and unbearable suffering' a just criterion for the deliberate termination of life of newborns with spina bifida? Hopeless suffering, with no means of alleviation, is not applicable in the acute phase of spina bifida in newborns, but to the chronic suffering that comes later on as the result of pain and discomfort experienced by the patient. There is a need for a nationwide discussion on (a) how can we determine when acute or chronic suffering become hopeless and unbearable, and on what basis should a given situation be regarded as an 'emergency situation'?; (b) what qualifies as a very severe form of spina bifida?; (c) what kind of care should be provided after the decision to withhold active care?
Assuntos
Tomada de Decisões , Eutanásia Ativa/ética , Qualidade de Vida , Disrafismo Espinal/complicações , Suspensão de Tratamento/ética , Ética Médica , Humanos , Recém-Nascido , Países BaixosRESUMO
CONTEXT: Longitudinal data on bone mineral density (BMD) in children and adolescents with Prader-Willi Syndrome (PWS) during long-term GH treatment are not available. OBJECTIVE: This study aimed to determine effects of long-term GH treatment and puberty on BMD of total body (BMDTB), lumbar spine (BMDLS), and bone mineral apparent density of the lumbar spine (BMADLS) in children with PWS. DESIGN AND SETTING: This was a prospective longitudinal study of a Dutch PWS cohort. PARTICIPANTS: Seventy-seven children with PWS who remained prepubertal during GH treatment for 4 years and 64 children with PWS who received GH treatment for 9 years participated in the study. INTERVENTION: The children received GH treatment, 1 mg/m(2)/day (â 0.035 mg/kg/d). MAIN OUTCOME MEASURES: BMDTB, BMDLS, and BMADLS was measured by using the same dual-energy x-ray absorptiometry machine for all annual measurements. RESULTS: In the prepubertal group, BMDTB standard deviation score (SDS) and BMDLSSDS significantly increased during 4 years of GH treatment whereas BMADLSSDS remained stable. During adolescence, BMDTBSDS and BMADLSSDS decreased significantly, in girls from the age of 11 years and in boys from the ages of 14 and 16 years, respectively, but all BMD parameters remained within the normal range. Higher Tanner stages tended to be associated with lower BMDTBSDS (P = .083) and a significantly lower BMADLSSDS (P = .016). After 9 years of GH treatment, lean body mass SDS was the most powerful predictor of BMDTBSDS and BMDLSSDS in adolescents with PWS. CONCLUSIONS: This long-term GH study demonstrates that BMDTB, BMDLS, and BMADLS remain stable in prepubertal children with PWS but decreases during adolescence, parallel to incomplete pubertal development. Based on our findings, clinicians should start sex hormone therapy from the age of 11 years in girls and 14 years in boys unless there is a normal progression of puberty.
Assuntos
Densidade Óssea , Hormônio do Crescimento Humano/uso terapêutico , Síndrome de Prader-Willi/tratamento farmacológico , Puberdade , Adolescente , Composição Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Criança , Pré-Escolar , Feminino , Hormônios Esteroides Gonadais/uso terapêutico , Humanos , Estudos Longitudinais , Masculino , Países Baixos , Síndrome de Prader-Willi/fisiopatologia , Puberdade/efeitos dos fármacos , Puberdade/fisiologia , Fatores de TempoRESUMO
We identified nine children with a leukoencephalopathy of similar type according to clinical and MRI findings. The patients included three affected sibling pairs. The age range was 3 to 19 years. The onset of the disease was in childhood; the course was both chronic-progressive and episodic. There were episodes of deterioration following infections and minor head traumas, and these could results in unexplained coma. In eight patients with advanced disease, MRI revealed a diffuse cerebral hemispheric leukoencephalopathy, in which increasing areas of the abnormal white matter had a signal intensity close to that of CSF on all pulse sequences. In one patient in the early stages of disease, initial MRI showed diffusely abnormal cerebral white matter, which only reached the signal characteristics of CSF at a later stage. In the patients in whom the disease was advanced, magnetic resonance spectroscopy (MRS) of the white matter showed an almost complete disappearance of all normal signals and the presence of glucose and lactate, compatible with the presence of mainly CSF and little brain tissue. Spectra of the cortex were much better preserved. However, in addition to the normal resonances, there were signals representing lactate and glucose. MRS of the white matter in the patient whose disease was at an early stage was much less abnormal. Autopsy in one patient confirmed the presence of extensive cystic degeneration of the cerebral white matter with reactive change and a preserved cortex. Typical involvement of pontine tegmental white matter was suggested by MRI and confirmed by autopsy. The disease probably has an autosomal recessive mode of inheritance, but the basic metabolic defect is not known.
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Encefalopatias/patologia , Encéfalo/patologia , Adolescente , Adulto , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Encefalopatias/diagnóstico , Encefalopatias/fisiopatologia , Criança , Pré-Escolar , Eletrofisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Medula Espinal/patologiaRESUMO
A 19-month-old girl presented with severe neurologic symptoms associated with exanthem subitum. Human herpesvirus type 7 (HHV-7) DNA was detected in the CSF and serum, and supported by serologic studies. The patient was diagnosed with encephalopathy due to an acute HHV-7 infection. Neuron-specific enolase in the CSF was strongly elevated during the acute stage of infection, suggesting that the encephalopathy was due to viral invasion of the brain.
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Encefalopatias/virologia , Infecções por Herpesviridae/líquido cefalorraquidiano , Herpesvirus Humano 7 , Encefalopatias/etiologia , DNA Viral/líquido cefalorraquidiano , Feminino , Infecções por Herpesviridae/complicações , Humanos , Lactente , Fosfopiruvato Hidratase/líquido cefalorraquidiano , Reação em Cadeia da PolimeraseRESUMO
OBJECTIVE: To determine the spectrum of clinical and MRI/1H MRS features of patients with fatty aldehyde dehydrogenase (FALDH) deficiency. BACKGROUND: The Sjogren-Larsson syndrome (SLS) was originally defined as a clinical triad consisting of ichthyosis, spastic di- or tetralegia, and mental retardation, with autosomal recessive inheritance. By now, both the deficiency of the enzyme FALDH, and the genetic mutations on chromosome 17 responsible for this deficiency, have been identified. SLS, defined by fibroblast FALDH deficiency, seems to be a much broader syndrome. METHODS: The clinical findings of 11 FALDH-deficient patients of different ages and one patient with the characteristic SLS-like ichthyosis, but without FALDH deficiency, were evaluated in relation to their cerebral MRI, and to 1H MRS in six patients. RESULTS: The severity of neurologic symptoms showed considerable variation. Fundoscopic perifoveal glistening dots and the characteristic SLS-like ichthyosis were present in all patients. Serial MRI findings showed evidence of retarded myelination and a variable degree of dysmyelination. 1H MRS showed an accumulation of free lipids in the periventricular white matter, even before the stage of visible dysmyelination. CONCLUSIONS: The neurologic consequences of FALDH deficiency show considerable variation. The characteristic pattern of ichthyosis and retinal degeneration are seen consistently, yet they are not pathognomonic. MRI and 1H MRS findings suggest an accumulation of long-chain fatty alcohol intermediates, resulting in retarded myelination and dysmyelination.
Assuntos
Aldeído Oxirredutases/deficiência , Síndrome de Sjogren-Larsson/patologia , Adolescente , Adulto , Encéfalo/patologia , Criança , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Radiografia , Retina/diagnóstico por imagem , Síndrome de Sjogren-Larsson/diagnóstico por imagem , Síndrome de Sjogren-Larsson/fisiopatologiaRESUMO
The corticospinal tract develops over a rather long period of time, during which malformations involving this main central motor pathway may occur. In rodents, the spinal outgrowth of the corticospinal tract occurs entirely postnatally, but in primates largely prenatally. In mice, an increasing number of genes have been found to play a role during the development of the pyramidal tract. In experimentally studied mammals, initially a much larger part of the cerebral cortex sends axons to the spinal cord, and the site of termination of corticospinal fibers in the spinal grey matter is much more extensive than in adult animals. Selective elimination of the transient corticospinal projections yields the mature projections functionally appropriate for the pyramidal tract. Direct corticomotoneuronal projections arise as the latest components of the corticospinal system. The subsequent myelination of the pyramidal tract is a slow process, taking place over a considerable period of time. Available data suggest that in man the pyramidal tract develops in a similar way. Several variations in the funicular trajectory of the human pyramidal tract have been described in otherwise normally developed cases, the most obvious being those with uncrossed pyramidal tracts. A survey of the neuropathological and clinical literature, illustrated with autopsy cases, reveals that the pyramidal tract may be involved in a large number of developmental disorders. Most of these malformations form part of a broad spectrum, ranging from disorders of patterning, neurogenesis and neuronal migration of the cerebral cortex to hypoxic-ischemic injury of the white matter. In some cases, pyramidal tract malformations may be due to abnormal axon guidance mechanisms. The molecular nature of such disorders is only beginning to be revealed.
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Tratos Piramidais/anormalidades , Tratos Piramidais/embriologia , Animais , Anormalidades Congênitas/embriologia , Desenvolvimento Embrionário , Humanos , Macaca mulatta/embriologiaRESUMO
PURPOSE: To report the ocular manifestations associated with the Sjögren-Larsson syndrome in a series of patients with proven fatty aldehyde dehydrogenase deficiency. To emphasize the clinical importance of the ophthalmological features of the Sjögren-Larsson syndrome. To discuss the metabolic disturbances that might give rise to the ophthalmological picture. METHODS: Fifteen patients with Sjögren-Larsson syndrome underwent a standardized ophthalmological examination. In patients of appropriate age, and who were able to cooperate, additional investigations were performed. RESULTS: All patients exhibited bilateral, glistening yellow-white crystalline deposits that were located in the innermost retinal layers and appeared during the first 2 years of life. Repeated fundus photography in individual patients showed that the dots became more numerous as the patients got older. Photophobia, subnormal visual acuity, myopia, and astigmatism were found in most of the patients. Fluorescein angiography was performed in three patients and showed a mottled hyperfluorescence of the retinal pigment epithelium, without leakage. Color vision, electroretinography, and electro-oculography could be performed in only a small number of patients and showed no abnormalities. Visual evoked potentials were found to be abnormal in six of eight patients. CONCLUSIONS: In Sjögren-Larsson syndrome, patients exhibit highly characteristic bilateral, glistening yellow-white retinal dots from the age of 1 to 2 years onward. The number of dots increases with age. The extent of the macular abnormality does not correlate with the severity of the ichthyosis or with the severity of the neurological abnormalities. A high percentage of patients shows additional ocular signs and symptoms, notably marked photophobia.
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Aldeído Oxirredutases/deficiência , Degeneração Macular/enzimologia , Síndrome de Sjogren-Larsson/enzimologia , Adolescente , Adulto , Astigmatismo/diagnóstico , Criança , Pré-Escolar , Eletrorretinografia , Potenciais Evocados Visuais , Feminino , Angiofluoresceinografia , Fundo de Olho , Humanos , Lactente , Degeneração Macular/diagnóstico , Masculino , Erros Inatos do Metabolismo/genética , Miopia/diagnóstico , Fotofobia/diagnóstico , Síndrome de Sjogren-Larsson/diagnóstico , Acuidade VisualRESUMO
The Sjögren-Larsson Syndrome (SLS) is a neurocutaneous disorder, caused by deficient activity of the microsomal enzyme fatty aldehyde dehydrogenase (FALDH). FALDH catalyzes the oxidation of medium- and long-chain fatty aldehydes to their corresponding carboxylic acids. SLS is diagnosed by demonstrating the enzyme deficiency or by mutation analysis of the FALDH gene, while laboratory investigations of plasma, urine, and cerebrospinal fluid do not reveal any diagnostic abnormality. Leukotriene (LT) B4 is a pro-inflammatory mediator synthesized from arachidonic acid. LTB4 is inactivated by microsomal omega-oxidation, successively yielding 20-OH-LTB4, 20-CHO-LTB4 and 20-COOH-LTB4. Since FALDH is involved in LTB4 degradation, we have analyzed LTB4 and its metabolites in urine and cerebrospinal fluid as well as the degradation capacity for LTB4 in fresh polymorphonuclear leukocytes (PMN) of SLS patients. The urinary concentrations of LTB4, 20-OH-LTB4 and 20-COOH-LTB4 are below the detection limit in healthy controls. The urine of all SLS patients (n=13) exhibited highly elevated concentrations of LTB4 and 20-OH-LTB4, while 20-COOH-LTB4 was absent. Cerebrospinal fluid levels of LTB4, 20-OH-LTB4 and 20-COOH-LTB4 were found to be normal (n=7). PMN isolated from four patients were shown to be unable to convert 20-OH-LTB4 to 20-COOH-LTB4. Our findings provide unambiguous evidence for defective LTB4 degradation in SLS patients, and offer new and non-invasive diagnostic tools. Moreover, they open new pathophysiological considerations, with the prospect of rational treatment strategies.
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Oxirredutases do Álcool/metabolismo , Leucotrieno B4/metabolismo , Síndrome de Sjogren-Larsson/enzimologia , Adolescente , Ácido Araquidônico/metabolismo , Criança , Pré-Escolar , Humanos , Ácidos Hidroxieicosatetraenoicos , Leucotrieno B4/análogos & derivadosRESUMO
In preterm and term infants, brainstem and middle latency auditory evoked responses (ABR and MLR) were obtained at 40 and 52 weeks conceptional age (CA) and at 5 years of age. A neurological and neuropsychological evaluation was performed at 5 years of age. To study the effect of preterm birth on the maturation of the ABR and MLR, the preterm infants were divided into early and late preterm groups. Only children with a normal neurodevelopmental outcome at 5 years of age were entered into the study. For ABR, the late preterm group showed significantly longer mean latencies IIc, III, V, and Vc when compared with the term group at 52 weeks CA. There was a trend to longer ABR latencies I in the early preterm group compared with the term group. At 52 weeks CA, the late preterm group showed longer mean interpeak latencies III-I and V-I when compared with the term as well as the early preterm group. At 5 years, the late preterm group showed significantly longer mean ABR latencies IIc and III when compared to the early preterm group. For MLR, the early preterm group showed significantly longer mean latencies of MLR component PO when compared with the term group at 40 weeks CA. At 52 weeks, the late preterm group also had longer mean MLR latencies P0 than the term group. At 5 years of age, the term group showed higher mean peak-to-peak amplitudes Na-P0 than the early as well as the late preterm group. To a large extent, the ABR results support the hypothesis that middle ear effusions in combination with retarded myelination of the central auditory pathway are responsible for the ABR differences found between term and preterm infants with a normal neurodevelopmental outcome at 5 years of age. The longer latencies and interpeak latencies found in late preterm infants when compared with early preterm infants might be explained by an augmented vulnerability of the auditory pathway between 30 and 34 weeks CA. The MLR differences found between term and preterm infants might be explained by a difference in the maturation of primary and nonprimary MLR components.
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Eletroencefalografia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Potenciais Evocados Auditivos/fisiologia , Recém-Nascido Prematuro/fisiologia , Tempo de Reação/fisiologia , Córtex Auditivo/crescimento & desenvolvimento , Vias Auditivas/crescimento & desenvolvimento , Tronco Encefálico/crescimento & desenvolvimento , Pré-Escolar , Feminino , Seguimentos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Testes Neuropsicológicos , Estudos Prospectivos , Valores de ReferênciaRESUMO
The goal of this study is to determine the neurodevelopmental profile of a group of low-risk preterm infants and to determine whether the potentially unfavourable outcome is due to a few infants with moderate to severe impairments or to a majority of infants with only slight impairments. In a prospective study 44 low-risk preterm infants, i.e. infants with a neonatal risk score indicating a favourable outcome, born between 25-34 weeks gestational age, and 18 healthy term infants were examined neurologically and tested neuropsychologically at 5 years of age. The more unfavourable outcome in the group of low-risk preterm infants compared with the term infants was largely attributable to a poorer outcome in 12 of the 44 low-risk preterm infants. The remaining low-risk preterm infants showed similar test scores compared with the term infants. From these results we conclude that the unfavourable neurodevelopmental outcome of low-risk preterm infants is due to moderate to severe impairment in a few low-risk preterm infants, rather than slight impairment in the majority. The low-risk preterm infants with an unfavourable outcome showed particular impairment on measures of visual-motor integration, concentration and auditory memory in combination with integrative functions.
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Encéfalo/fisiologia , Deficiências do Desenvolvimento/diagnóstico , Recém-Nascido Prematuro/fisiologia , Peso ao Nascer , Encéfalo/anormalidades , Pré-Escolar , Deficiências do Desenvolvimento/etiologia , Seguimentos , Humanos , Lactente , Recém-Nascido , Transtornos das Habilidades Motoras/diagnóstico , Exame Neurológico/estatística & dados numéricos , Testes Neuropsicológicos/estatística & dados numéricos , Estudos Prospectivos , Transtornos Psicomotores/diagnóstico , Medição de Risco , Índice de Gravidade de Doença , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The prognosis of craniopharyngioma in children after subtotal surgical removal, followed by irradiation of remaining tumour with 50 Gy, is better than usually reported. In our subjects we found a relapse rate of 5% in the last 20 years. The treatment of recurrences forms a special problem because the possibilities of adjuvant radiotherapy are restricted. We report on a chemotherapeutic treatment after multiple or very rapid recurrences of craniopharyngioma in four children. METHODS: Four children experienced their first tumour recurrence at respectively 3, 8, 50 and 59 months after the initial treatment. New neurosurgical attempts to remove the recurring tumour, and in one patient a second course of radiotherapy, were performed, but there were two or more recurrences in these children, resulting in further restriction of surgical or radiotherapeutical possibilities. Chemotherapy was given, consisting of five intravenous ambulatory courses of Adriamycin (doxorubicin) (33 mg/m2/day, continuously over 3 days) together with oral CCNU (lomustine) (80 mg/m2 at day 1) at 6-weeks intervals. RESULTS: After the chemotherapy there was no further tumour recurrence after 12, 10, 3 and 3 years respectively. In the third patient a cystic relapse occurred after 3 years' remission. In the fourth patient a complete regression was observed of the cystic part of the tumour. The side-effects of the chemotherapy consisted of alopecia and bone marrow depression. No signs of cardiomyopathy have been found. CONCLUSION: Treatment of recurrent craniopharyngioma in children by chemotherapy with anthracyclines and nitrourea-derivates may be effective.
Assuntos
Antineoplásicos/uso terapêutico , Craniofaringioma/tratamento farmacológico , Doxorrubicina/uso terapêutico , Lomustina/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Adolescente , Pré-Escolar , Terapia Combinada , Craniofaringioma/diagnóstico por imagem , Craniofaringioma/cirurgia , Feminino , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Homovanillic acid (HVA) is a metabolite of dopamine, reflecting central dopamine metabolism, primarily situated in the striatum. Low HVA concentrations in the cerebrospinal fluid (CSF) may indicate metabolic deficiencies in the pathways of the biosynthesis or catabolism of dopamine. In this retrospective study, we investigated the clinical presentation of patients whose HVA concentration in the CSF had been determined routinely after spinal taps for a variety of clinical reasons. A decrease of HVA concentration in the CSF, due to a defect in the biosynthesis or reuptake of dopamine, is expected to cause extrapyramidal features. However, we found a remarkable variability in the clinical symptoms. Similarly, a decreased HVA concentration in the CSF failed to coincide with specific abnormalities at neuroimaging. In view of the diversity of the clinical presentation and in the absence of specific enzyme deficiencies, a decrease of HVA may be due to dysfunction of dopamine neurons, not resulting in specific extrapyramidal symptoms. Thus, with the exception of diseases associated with a specific enzyme deficiency in the metabolic pathways involving dopamine, a decrease of HVA concentration in the CSF is mainly a secondary or epiphenomenon in a variety of clinical conditions.