46 research outputs found
Treatment of paediatric pontine glioma with oral trophosphamide and etoposide
To evaluate the overall survival of paediatric patients with pontine gliomas treated with oral trophosphamide and etoposide. Patients between 3 and 17 years of age with either typical diffuse pontine glioma on MRI or histologically proven anaplastic astrocytoma/glioblastoma multiforme located in the pons, were eligible. Treatment consisted of oral trophosphamide 100 mg m−2 day−1 combined with oral etoposide at 25 mg m−2 day−1 starting simultaneously with conventional radiation. Twenty patients were enrolled (median age 6 years, male : female=9 : 11). Surgical procedures included: no surgery: five, open biopsy: three, stereotactic biopsy: six, partial resection: three, and sub-total resection: three. Histological diagnoses included pilocytic astrocytoma: one, astrocytoma with no other specification: three, anaplastic astrocytoma: three, glioblastoma multiforme: eight, no histology: five. The most frequent side effects were haematologic and gastrointestinal. There was no toxic death. The response to combined treatment in 12 evaluable patients was: complete response: 0, partial response: three, stable disease: four, and progressive disease: five. All tumours progressed locally and all patients died. The overall median survival was 8 months. The overall survival rates at 1 and 4 years were: 0.4 and 0.05 respectively. This was not different from a control group of patients documented in the same population. Oral trophosphamide in combination with etoposide did not improve survival of pontine glioma patients. The treatment was well tolerated and should be evaluated for more chemoresponsive paediatric malignancies
Perinatal asphyxia: current status and approaches towards neuroprotective strategies, with focus on sentinel proteins
Delivery is a stressful and risky event menacing the newborn. The mother-dependent respiration has to be replaced by autonomous pulmonary breathing immediately after delivery. If delayed, it may lead to deficient oxygen supply compromising survival and development of the central nervous system. Lack of oxygen availability gives rise to depletion of NAD+ tissue stores, decrease of ATP formation, weakening of the electron transport pump and anaerobic metabolism and acidosis, leading necessarily to death if oxygenation is not promptly re-established. Re-oxygenation triggers a cascade of compensatory biochemical events to restore function, which may be accompanied by improper homeostasis and oxidative stress. Consequences may be incomplete recovery, or excess reactions that worsen the biological outcome by disturbed metabolism and/or imbalance produced by over-expression of alternative metabolic pathways. Perinatal asphyxia has been associated with severe neurological and psychiatric sequelae with delayed clinical onset. No specific treatments have yet been established. In the clinical setting, after resuscitation of an infant with birth asphyxia, the emphasis is on supportive therapy. Several interventions have been proposed to attenuate secondary neuronal injuries elicited by asphyxia, including hypothermia. Although promising, the clinical efficacy of hypothermia has not been fully demonstrated. It is evident that new approaches are warranted. The purpose of this review is to discuss the concept of sentinel proteins as targets for neuroprotection. Several sentinel proteins have been described to protect the integrity of the genome (e.g. PARP-1; XRCC1; DNA ligase IIIα; DNA polymerase β, ERCC2, DNA-dependent protein kinases). They act by eliciting metabolic cascades leading to (i) activation of cell survival and neurotrophic pathways; (ii) early and delayed programmed cell death, and (iii) promotion of cell proliferation, differentiation, neuritogenesis and synaptogenesis. It is proposed that sentinel proteins can be used as markers for characterising long-term effects of perinatal asphyxia, and as targets for novel therapeutic development and innovative strategies for neonatal care
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Children born prematurely have atypical Sensory Profiles
ObjectiveTo determine if children born prematurely exhibit atypical responses to normally occurring sensory stimuli, as measured by the Sensory Profile.Study designThis is a cross-sectional study of children born at 32 weeks gestation, followed at 1 to 8 years of age. The Sensory Profile questionnaire was completed by each child's primary caregiver. The overall Sensory Profile was considered atypical if any quadrant or section score was >2 s.d. from the mean of the Sensory Profile validation group. Bivariate analyses were performed to determine associations between risk factors for adverse neurodevelopment and overall atypical Sensory Profiles. A section or quadrant was considered atypical if its score was >2 s.d. from the mean. A test of proportions was used to compute observed versus expected scores for each section and quadrant (Sensory Profile scores were based on a normal distribution so one would expect approximately 95% of participants to score within 2 s.d. of the mean).ResultOf our 107 participants, 39% had an atypical score in at least one section or quadrant. No specific perinatal or neonatal risk factors were associated with atypical overall Sensory Profiles (P0.05 for all). Children born prematurely were at risk of having atypical scores in the auditory, tactile and vestibular processing sections, and in the four Sensory Profile quadrants (P<0.05).ConclusionChildren born prematurely exhibit atypical sensory behaviors on the Sensory Profile. Further investigation to understand the underlying neural mechanisms and to develop effective interventions are critical to support neurodevelopment for these children