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Buenos Aires, Argentina

Schaiquevich P.,CONICET | Buitrago E.,University of Buenos Aires | Ceciliano A.,Office of Laboratory Animal Care | Fandino A.C.,Office of Laboratory Animal Care | And 4 more authors.
Retina | Year: 2012

PURPOSE: To characterize the vitreous and plasma pharmacokinetics of topotecan after ophthalmic artery infusion (OAI) subsequent to superselective artery catheterization and to compare it with periocular injection (POI). METHODS: The ophthalmic artery of 4 pigs was catheterized and 1 mg of topotecan infused over a period of 30 minutes. The contralateral eye was subsequently used for administering topotecan by POI. Serial vitreous specimens were obtained by microdialysis and plasma samples collected and assayed for total and lactone topotecan. RESULTS: Maximum total topotecan concentration in the vitreous (median, range) was significantly higher after OAI compared with POI (131.8 ng/mL [112.9-138.7] vs. 13.6 ng/mL [5.5-15.3], respectively; P < 0.005). Median vitreous exposure calculated as area under the curve for total topotecan attained after OAI was significantly higher than after POI (299.8 ng•hour/mL [247.6-347.2] and 48.9 ng•hour/mL [11.8-63.4], respectively; P < 0.05). The vitreous to plasma exposure ratio was 29 after OAI and 3.4 after POI. Systemic exposure for total topotecan was low after both modalities of administration, with a trend to be lower after OAI compared with POI (10.6 ng•hour/mL [6.8-13.4] vs. 18.7 ng•hour/mL [6.3-21.7]; P = 0.54). CONCLUSION: Superselective OAI resulted in significantly higher vitreous concentrations and exposure and a trend toward lower systemic exposure than POI. Copyright © by Ophthalmic Communications Society, Inc. Unauthorized reprodution of this article is prohibited. Source

Siegel D.H.,Medical College of Wisconsin | Tefft K.A.,University of Kansas Medical Center | Kelly T.,Medical College of Wisconsin | Johnson C.,Medical College of Wisconsin | And 11 more authors.
Stroke | Year: 2012

Background and Purpose-: PHACE is an acronym for posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities. Several case reports of arterial ischemic stroke (AIS) in individuals with PHACE have been published, but risk factors for AIS in PHACE have not been clearly defined. The objective of this article is to review all cases of stroke in PHACE in children and describe clinical characteristics that may be associated with an increased risk of AIS. Methods-: A literature and registry search was conducted to identify patients with PHACE who had experienced AIS. Data were analyzed to determine age of onset, presenting signs and symptoms, and clinical features among this cohort compared with PHACE without AIS. Results-: Twenty-two individuals with PHACE and AIS were identified. Imaging of the arteries of the head and neck was reported in 20 of 22. Narrowing or nonvisualization of at least 1 great cerebral vessel was present in 19 of 20 and of those, 15 had ≥2 vessels involved. Aortic arch anomalies were reported in 13 of 22 individuals. Conclusions-: Aplasia, hypoplasia, or occlusion of a major cerebral artery appears to be a significant risk factor for AIS in children with PHACE, especially when >1 vessel is involved or if there is coarctation of the aorta. © 2012 American Heart Association, Inc. Source

Cho T..-J.,Seoul National University | Matsumoto K.,Gifu University | Fano V.,Hospital de Pediatria JP Garrahan | Dai J.,RIKEN | And 12 more authors.
American Journal of Medical Genetics, Part A | Year: 2012

Heterozygous missense mutations of transient receptor potential vanilloid 4 channel (TRPV4) cause a spectrum of skeletal disorders, including brachyolmia, spondylometaphyseal dysplasia Kozlowski type, metatropic dysplasia, parastremmatic dysplasia, and spondyloepimetaphyseal dysplasia Maroteaux type. Similarly, heterozygous missense mutations of TRPV4 cause a spectrum of peripheral neuropathy, including hereditary motor and sensory neuropathy type IIC, congenital spinal muscular atrophy, and scapuloperoneal spinal muscular atrophy. There are no apparent differences in the amino acid positions affected or type of change predicted by the TRPV4 mutations responsible for the two disease spectrums; nevertheless, no fundamental phenotypic overlap has been shown between the two spectrums. Here, we report on three patients who had both skeletal dysplasia and peripheral neuropathy caused by heterozygous TRPV4 missense mutations. The skeletal and neurologic phenotypes of these patients covered the wide spectrum of reported TRPV4-pathies (disease caused by TRPV4 mutations). The molecular data are complementary, proving that "neuropathic" mutations can cause skeletal dysplasia but also the "skeletopathic" mutations can lead to neuropathies. Our findings suggest that pathogenic mechanisms of TRPV4-pathies in skeletal and nervous systems are not always mutually exclusive and provide further evidence that there is no clear genotype-phenotype correlation for either spectrum. Co-occurrence of skeletal dysplasia and degenerative neuropathy should be kept in mind in clinical practice including diagnostic testing, surgical evaluation, and genetic counseling. © 2012 Wiley Periodicals, Inc. Source

Oberlin O.,Institute Gustave Roussy | Rey A.,Institute Gustave Roussy | Sanchez De Toledo J.,Hospital Universitari Vall dHebron | Martelli H.,Hopital de Bicetre | And 8 more authors.
Journal of Clinical Oncology | Year: 2012

Purpose: MMT95 was the fourth of a series of International Society of Pediatric Oncology (SIOP) collaborations for children with high-risk nonmetastatic soft tissue sarcoma (STS). The principal objective was to explore survival advantage for an intensified chemotherapy strategy in a randomized trial. Patients and Methods: From July 1995 to June 2003, 457 previously untreated patients with incompletely resected embryonal rhabdomyosarcoma (RMS), undifferentiated sarcoma, and soft tissue primitive neuroectodermal tumor at all sites except paratesticular, vagina, and uterus, or with alveolar RMS were randomly assigned to receive either ifosfamide, vincristine, and dactinomycin (IVA) or a six-drug combination (IVA plus carboplatin, epirubicin, and etoposide) both delivered over 27 weeks. Cumulative doses were as follows: ifosfamide 54 g/m 2 (both arms), epirubicin 450 mg/m 2, etoposide 1,350 mg/m 2 (six-drug regimen). Poor responders after three courses of IVA were to be switched to the other arm. Delivery of radiotherapy was determined according to site and/or response to chemotherapy with or without surgery. Results: Overall survival (OS) for all patients was 81% (95% CI, 77% to 84%) at 3 years. No significant difference in outcome in either OS or event-free survival was noted between the two arms (3-year OS: 82% [95% CI, 76% to 86%] for IVA and 80% [95% CI, 74% to 85%] for the six-drug arm). Toxicity was significantly greater (infection, myelosuppression, and mucositis) in the six-drug arm. Overall burden of local therapy was consistent with data from previous SIOP studies and showed no difference between the two chemotherapy regimens. Conclusion: Intensification of chemotherapy for nonmetastatic RMS and other chemotherapy-sensitive STS provides no survival advantage or reduction in the intensity of local therapy and adds toxicity. © 2012 by American Society of Clinical Oncology. Source

Dunkel I.J.,Sloan Kettering Cancer Center | Chan H.S.L.,Hospital for Sick Children | Jubran R.,Childrens Hospital of Los Angeles | Chantada G.L.,Hospital de Pediatria JP Garrahan | And 4 more authors.
Pediatric Blood and Cancer | Year: 2010

Background. Stage 4b retinoblastoma (central nervous system metastatic disease) has been lethal in virtually all cases reported. Here we describe a series of eight patients treated with intensive chemotherapy, defined as the intention to include highdose chemotherapy with autologous hematopoietic stem cell rescue. Procedure. Induction chemotherapy included cyclophosphamide and/or carboplatin with a topoisomerase inhibitor. Highdose chemotherapy regimens were carboplatin and thiotepa with or without etoposide (n=3) or carboplatin, etoposide, and cyclophosphamide (n=2). Results. Seven patients had leptomeningeal disease and one patient had only direct extension to the CNS via the optic nerve. Three patients had stage 4b disease at the time of original diagnosis of the intra-ocular retinoblastoma; five had later onset at a median of 12 months (range 3-69 months). One patient died of toxicity (septicemia and multi-organ system failure) during induction and two had disease progression prior to high-dose chemotherapy. Five patients received high-dose chemotherapy at a median of 6 months (range 4-6) post-diagnosis of stage 4b disease. Two patients survive event-free at 40 and 101 months; one was irradiated following recovery from the high-dose chemotherapy. Conclusions. Intensive multimodality therapy may be beneficial for some patients with stage 4b retinoblastoma. Longer follow-up will determine whether it has been curative. © 2010 Wiley-Liss, Inc. Source

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