Fatal asphyxiations in children involving drawstrings on clothing.

Injuries account for more deaths and hospital admissions among children and adolescents than all diseases combined. The authors report two deaths by asphyxiation that resulted from drawstrings on the children's clothing becoming entangled on slides. Although such incidents are not common, they are preventable. The authors urge physicians to counsel parents and guardians to remove drawstrings from children's clothing, and they call upon the government and the clothing industry to work toward improving the safety standards for the design, manufacture and importation of children's clothing and banning the sale of children's clothing with drawstrings in Canada. In addition, they provide several resources for readers interested in helping reduce playground hazards in their communities.     

Decreased efficacy of levodopa with carbidopa in parkinsonian patients after adrenal-to-caudate implants

We studied 6 parkinsonian patients 6 weeks after unilateral adrenal-to-caudate implants. We withheld medications the night before each of 2 study days and gave the patients a single test dose of either a combination of levodopa and carbidopa, or levodopa alone in double-blind random order. We administered the modified Columbia scale, objective measurements of rigidity and movement velocity, and the pegboard test at regular intervals after the single test dose. The results revealed that the improvements in performance recorded by the Columbia scale and the pegboard test were significantly less on the side contralateral to the operation when patients received carbidopa, whereas there was no significant difference in performance between the 2 observations on the ipsilateral side. Carbidopa apparently crossed the disrupted blood-brain barrier and lowered the efficacy of levodopa.     

Cerebrospinal fluid myelin basic protein as a prognostic marker in patients with head injury

Despite increasing interest in identifying biochemical and serologic markers to judge the severity of closed head injury in comatose patients, clinical variables remain the most readily available methods for assessing prognosis. In a series of 35 severely head-injured comatose patients, the cerebrospinal fluid (CSF) level of myelin basic protein (MBP) was analyzed by radioimmunoassay. MBP levels during the first week after injury were significantly correlated with the Glasgow outcome score at 7 days (p less than .005), 3 months (p less than .005), and 6 months (p less than .05) postinjury. Measurement of CSF MBP appears to be a useful laboratory adjunct to clinical assessment, for judging the outcome of severely head-injured patients.     

TRAIL triggers apoptosis in human malignant glioma cells through extrinsic and intrinsic pathways

Many malignant glioma cells express death receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), yet some of these cells are resistant to TRAIL. Here, we examined signaling events in TRAIL-induced apoptosis and searched for therapeutic agents that could overcome TRAIL resistance in glioma cells. TRAIL induced apoptosis through death receptor 5 (DR5) and was mediated by caspase-8-initiated extrinsic and intrinsic mitochondrial pathways in sensitive glioma cell lines. TRAIL also triggered apoptosis in resistant glioma cell lines through the same pathways, but only if the cells were pretreated with chemotherapeutic agents, cisplatin, camptothecin and etoposide. Previous studies suggested that this was due to an increase in DR5 expression in wild-type TP53 cells, but this mechanism did not account for cells with mutant TP53. Here, we show that a more general effect of these agents is to downregulate caspase-8 inhibitor c-FLIP(S) (the short form of cellular Fas-associated death domain-fike interleukin-1-converting enzyme-inhibitory protein) and up-regulate Bak, a pro-apoptotic Bcl-2 family member, independently of cell's TP53 status. Furthermore, we showed that TRAIL alone or in combination with chemotherapeutic agents, induced apoptosis in primary tumor cultures from patients with malignant gliomas, reinforcing the potential of TRAIL as an effective therapeutic agent for malignant gliomas.     

Glutathione levels and chemosensitizing effects of buthionine sulfoximine in human malignant glioma cells

Summary Biopsy samples and cultured cells derived from them were obtained from 39 patients with malignant glioma and were analyzed for 1) glutathione (GSH) content; 2) sensitivity to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and/or nitrogen mustard (HN2) treatment and 3) the effect of buthionine sulfoximine (BSO) treatment on BCNU and/or HN2 cytotoxicity. The average GSH concentration of biopsy specimens was lower than those of cultured cells (2.36±0.44 vs. 11.42±2.32 nmol/10⁶ cells). While some of the tumor specimens were sensitive to either BCNU or HN2, the majority were resistant to both. However, 8 of 23 tumors tested showed enhanced sensitivity to BCNU following treatment with BSO. Five of 17 tumors were similarly sensitized to HN2 by BSO. These results suggest that BSO chemosensitization may be of value for certain patients and that screening assays may help identify treatment-sensitive individuals.     

Human autologous in vitro models of glioma immunogene therapy using B7-2, GM-CSF,and IL12

BACKGROUND: Cancer immunogene therapy is based on vaccination with radiated, autologous tumor cells transduced with immunostimulatory genes. To help determine an optimal glioma immunogene therapy strategy, we stimulated lymphocytes with autologous human glioma cells transduced with B7-2 (CD86), granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or interleukin-12 (IL12). METHODS: A human glioma-derived cell culture (Ed147.BT) was transduced with B7-2, GM-CSF, and/or IL12 using retroviral vectors. Autologous peripheral blood mononuclear cells (PBMC) were co-cultured with irradiated gene-transduced tumor alone or a combination of radiated wild type and gene-transduced cells. Peripheral blood mononuclear cells proliferation was determined by serial cell counts. Peripheral blood mononuclear cells phenotype was assessed by flow cytometry for CD4, CD8, and CD16. Anti-tumor cytotoxicity was determined by chromium-51 (51Cr) release assay. RESULTS: Peripheral blood mononuclear cells cell numbers all decreased during primary stimulation but tumor cells expressing B7-2 or GM-CSF consistently caused secondary proliferation. Tumors expressing B7-2 and GM-CSF or B7-2, GM-CSF, and IL12 consistently increased PBMC CD8+ (cytotoxic T) and CD16+ (natural killer) percentages. Interestingly, anti-tumor cytotoxicity only exceeded that of PBMC stimulated with wild type tumor alone when peripheral blood mononuclear cells were stimulated with both wild type tumor and B7-2/GM-CSF- (but not IL12) transduced cells. CONCLUSIONS: PBMC proliferation and phenotype is altered as expected by exposure to immunostimulatory gene-transduced tumor. However, transduced tumor cells alone do not stimulate greater anti-tumor cytotoxicity than wild type tumor. Only B7-2/GM-CSF-transduced cells combined with wild type produced increased cytotoxicity. This may reflect selection of tumor subclones with limited antigenic spectra during retrovirus-mediated gene transfer.     

Association between angiotensin-converting enzyme and Alzheimer disease

BACKGROUND: Angiotensin-converting enzyme has been reported to show altered activity in patients with neurologic diseases. An insertion-deletion polymorphism in ACE has recently been linked to heart disease, cerebrovascular disease, and AD. OBJECTIVE: To determine whether the angiotensin-converting enzyme (ACE) is associated with risk of Alzheimer disease (AD). METHODS: We investigated the ACE polymorphism as a potential risk factor for AD in 151 patients with AD and 206 ethnically matched controls from Russia and in 236 patients with AD and 169 controls from North America by means of allele association methods and logistic regression. RESULTS: None of the ACE genotypes was associated with increased susceptibility to AD in the total sample or in subsets stratified by apolipoprotein E gene (APOE) epsilon4 status. However, the D allele was more frequent among AD cases between ages 66 and 70 years compared with controls in both the Russian (P = .02) and North American (P = .001) datasets. In this age group, the effect of D (odds ratio, 11.2; 95% confidence interval, 2.9-44.0) appeared to be independent of and equal or greater in magnitude to the effect of APOE epsilon4 (odds ratio, 7.8; 95% confidence interval, 3.5-7.4). CONCLUSIONS: Our results suggest that APOE and ACE genotypes may be independent risk factors for late-onset AD, but the ACE association needs to be confirmed in independent samples in which the time and extent of vascular cofactors can be assessed.