Basic fibroblast growth factor protects striatal neurons in vitro from NMDA-receptor mediated excitotoxicity.

Basic fibroblast growth factor (bFGF) promotes the survival and outgrowth of neurons. In this study the neuroprotective effects of bFGF were examined in 12-18-day-old cultured striatal neurons exposed to glutamic acid, kainic acid (KA), and quinolinic acid (QA), an N-methyl-D-aspartate (NMDA)-receptor agonist. Results showed that preincubation with bFGF (6 pM) from the day of plating significantly increased the survival of striatal neurons treated for 3 h with glutamate (3 mM) or QA (1 mM), but had little effect on KA (1 mM) induced toxicity. Moreover, maximum protection by bFGF against glutamate neurotoxicity was observed in cultures treated as little as 2 h before glutamate exposure. These results show that bFGF markedly protects striatal neurons from NMDA-receptor induced neurotoxicity.     

13-cis-retinoic acid (NSC 122758) in the treatment of children with metastatic neuroblastoma unresponsive to conventional chemotherapy: Report from the childrens cancer study group

The Childrens Cancer Study Group evaluated daily oral 13-cis-retinoic acid to determine its therapeutic efficacy in 28 children with advanced neuroblastoma refractory to conventional therapy. Cheilitis and fissured lips were the most common side effects; however, fewer than 50% of the patients experienced any toxicity. Two of twenty-two evaluable children demonstrated positive response to therapy. In one case, a child received the drug for 11 months. Seventeen patients demonstrated progressive disease within 28 days of the start of treatment. Three other patients with stable disease, or removed from study at day 28, were considered nonresponsive. Our data demonstrate that, when given as a single daily oral dose of 100 mg/m², 13-cis-retinoic acid does not have significant activity in children with advanced neuroblastoma. © 1992 Wiley-Liss, Inc.     

Integrating complementary and alternative medicine instruction into health professions education: organizational and instructional strategies.

A few years ago, the National Institutes of Health National Center for Complementary and Alternative Medicine funded a program called the Complementary and Alternative Medicine (CAM) Education Project. Grantees were 14 medical and nursing schools and the American Medical Student Association, which funded six additional medical schools. Grants were awarded in cohorts of five per year in 2000, 2001, and 2002-2003.The R25 grant recipients identified several major themes as crucial to the success of integrating CAM into health professions curricula. The rationale for integrating CAM curricula was in part to enable future health professionals to provide informed advice as patients dramatically increase the use of CAM. Success of new CAM education programs relied on leadership, including top-down support from institutions' highest administrators. Formal and informal engagement of key faculty and opinion leaders raised awareness, interest, and participation in programs. A range of faculty development efforts increased CAM-teaching capacity. The most effective strategies for integration addressed a key curriculum need and used some form of evidence-based practice framework. Most programs used a combination of instructional delivery strategies, including experiential components and online resources, to address the needs of learners while promoting a high level of ongoing interest in CAM topics. Institutions noted several benefits, including increased faculty development activities, the creation of new programs, and increased cross- and inter-university collaborations. Common challenges included the need for qualified faculty, crowded and changing curricula, a lack of defined best practices in CAM, and post-grant sustainability of programs.     

Potential usefulness of basic fibroblast growth factor as a treatment for stroke

Within the past few years, a growing body of evidence has accumulated indicating that exogenously administered neurotrophic growth factors may limit the extent of acute ischemic neural injury and enhance functional neurorecovery following stroke. One of the most widely studied growth factor in this regard is basic fibroblast growth factor (bFGF). In preclinical studies, bFGF administered intravenously within hours after the onset of ischemia reduces infarct size, presumably due to direct protection of cells at the borders (penumbra) of cerebral infarction. On the other hand, if bFGF is administered intracisternally starting at one day after ischemia, infarct size is not reduced, but recovery of sensorimotor function of the impaired limbs is increased, presumably due to enhancement of new neuronal sprouting and synapse formation in the intact uninjured brain. Clinical trials of the intravenous administration of bFGF as a cytoprotective agent in acute stroke are in progress. Trials of the delayed administration of bFGF as a recovery-promoting agent in subacute stroke are anticipated.     

Effect of duration of treatment on treatment outcome for patients with clear-cell sarcoma of the kidney: a report from the National Wilms' Tumor Study Group.

PURPOSE: To evaluate the effect of conventional and standard (ST) versus pulse-intensive (PI) chemotherapy and short-duration versus long-duration chemotherapy on relapse-free survival (RFS) and overall survival rates of patients with clear-cell sarcoma of the kidney (CCSK) entered onto the National Wilms' Tumor Study (NWTS)-4. PATIENTS AND METHODS: The 5-year and 8-year RFS rates were determined for patients with CCSK treated on the NWTS-4. After August 6, 1986, 40 previously untreated children younger than 16 years with CCSK were randomly assigned, after the completion of 6 months of chemotherapy, to discontinue (short) or continue 9 additional months (long) of treatment with chemotherapy regimens that included vincristine and either divided-dose (ST) courses (5 days) or single-dose (PI) treatment with dactinomycin and divided-dose (ST) courses (3 days) or single-dose (PI) treatment with doxorubicin. RESULTS: For patients with CCSK, the 5- and 8-year RFS rates were 65.2% and 60.6%, respectively, for patients randomly assigned to the short chemotherapy and 87.8% (both 5- and 8-year RFS) for patients randomly assigned to the long chemotherapy (P =.08). The overall survival rates for patients at 5 and 8 years were 95.5% and 85.9%, respectively, for the short chemotherapy and 87.5% (both 5- and 8-year overall survival) for the long chemotherapy (P =.99). In NWTS-4, the overall survival rates for patients with CCSK improved from NWTS-3 (83% v 66.9% at 8 years, respectively; P <.01). CONCLUSION: CCSK patients exhibit an improved RFS from a longer course of therapy when using vincristine, doxorubicin, and dactinomycin, but their long-term survival is unchanged compared with patients receiving 6 months of therapy. The overall survival rates for patients with CCSK have improved from NWTS-3.     

Motor recovery and cortical reorganization after constraint-induced movement therapy in stroke patients: a preliminary study

Constraint-induced movement therapy (CIMT) is a physical rehabilitation regime that has been previously shown to improve motor function in chronic hemiparetic stroke patients. However, the neural mechanisms supporting rehabilitation-induced motor recovery are poorly understood. The goal of this study was to assess motor cortical reorganization after CIMT using functional magnetic resonance imaging (fMRI). In a repeated-measures design, 4 incompletely recovered chronic stroke patients treated with CIMT underwent motor function testing and fMRI. Five age-matched normal subjects were also imaged. A laterality index (LI) was determined from the fMRI data, reflecting the distribution of activation in motor cortices contralateral compared with ipsilateral to the moving hand. Pre-intervention fMRI showed a lower LI during affected hand movement of stroke patients (LI = 0.23+/-0.07) compared to controls (LI unaffected patient hand = 0.65+/-0.10; LI dominant normal hand = 0.65+/-0.11; LI nondominant normal hand = 0.69+/-0.11; P < 0.05) due to trends toward increased ipsilateral motor cortical activation. Motor function testing showed that patients made significant gains in functional use of the stroke-affected upper extremity (detected by the Motor Activity Log) and significant reductions in motor impairment (detected by the Fugl-Meyer Stroke Scale and the Wolf Motor Function Test) immediately after CIMT, and these effects persisted at 6-month follow-up. The behavioral effects of CIMT were associated with a trend toward a reduced LI from pre-intervention to immediately post-intervention (LI = -0.01+/-0.06, P = 0.077) and 6 months post-intervention (LI = -0.03+/-0.15). Stroke-affected hand movement was not accompanied by mirror movements during fMRI, and electromyographic measures of mirror recruitment under simulated fMRI conditions were not correlated with LI values. These data provide preliminary evidence that gains in motor function produced by CIMT in chronic stroke patients may be associated with a shift in laterality of motor cortical activation toward the undamaged hemisphere.