Regional brain atrophy in progressive supranuclear palsy and Lewy body disease

There have been no previous three-dimensional volumetric studies of regional brain atrophy in patients with pathologically confirmed progressive supranuclear palsy (PSP). Postmortem cortical and subcortical volumes were compared with neuropathology in 9 patients with PSP, 15 patients with Parkinson's disease, 10 patients with dementia with Lewy bodies, and 23 controls. Cases with the neuritic pathology of Alzheimer's disease were excluded. The topography of brain atrophy differed according to clinicopathological phenotype. Patients with Parkinson's disease had atrophy confined to the amygdala. Atrophy of the frontal lobe was found in both PSP and dementia with Lewy bodies and correlated with increasing neurofibrillary tangle or Lewy body densities, respectively. Patients with PSP could be differentiated by their marked atrophy of the internal globus pallidus. Further analysis of variance revealed that trends for greater frontal lobe atrophy correlated with clinical dementia in PSP, whereas both greater frontal and hippocampal atrophy and higher densities of Lewy bodies and Lewy neurites correlated with clinical dementia in cases with Lewy bodies. The present study provides evidence for selective regional atrophy that correlates with the underlying pathology of PSP and Lewy body disease.     

Do weekends or evenings matter in a pediatric intensive care unit?

OBJECTIVE: To assess what independent influence, if any, weekend or evening admission to a pediatric intensive care unit (PICU) staffed 24 hrs/day, 7 days/wk by in-house, board-certified pediatric intensivists might have on mortality. DESIGN AND PATIENTS: A retrospective study of 5,968 consecutive admissions to the PICU from August 1996 to December 2003 for patients aged 0 days to 21 yrs. SETTING: A single, 14-bed, multidisciplinary PICU at an academic medical center. MEASUREMENTS: Standardized mortality ratios of observed-to-predicted mortality were derived with their corresponding p values. Multivariate logistic regression was used to test the independent effect of weekend admission, weekend discharge/death, and evening PICU admission on mortality for the entire sample and, separately, for only emergency admissions, controlling for other significant predictor variables or interaction terms. RESULTS: Overall, crude mortality was significantly higher on the weekend (weekday, 2.2%; weekend, 5.0% [p = .0000]) and in the evening (day, 2.1%; evening, 3.8% [p = .0004]). Assessing the entire sample using multivariate logistic regression, neither weekend admission (p = .146), weekend discharge/death (p = .348), nor evening PICU admission (p = .711) showed a significant relationship with mortality controlling for other significant factors. Limiting the scope to the emergency admissions subset, neither weekend admission (p = .135), weekend discharge/death (p = .278), nor evening PICU admission (p = .867) were significant predictors of mortality. Weekend and evening admissions differed in important ways from weekday and daytime admissions, making simple comparisons of crude mortality rates inappropriate. Weekend and evening admissions were more likely to be emergency, nonoperative patients; have a lower Pediatric Risk of Mortality III score but have a higher overall predicted mortality risk; and differ in the distributions of patients by primary diagnosis. CONCLUSIONS: Using multivariate logistic regression to control for important clinical differences, neither weekend admission, weekend discharge/death, nor evening admission had a significant independent effect on mortality risk in the entire sample or for the emergency patient subset. Our findings are consistent with previous work demonstrating the benefit of intensive care units staffed 24 hrs/day, 7-days/wk by in-house, board-certified intensivists.     

关于人眼视力发展的非线性成长率理论

目的使用非线性成长率理论分析人眼视力发展规律。方法使用高斯光学及成像方程推导出两个参数：屈光状态改变率（M）及眼轴成长率（N），用以预测MOS（初始近视）、年龄（A^＊）及其后视力的发展情况。结果当有效焦距F=（21-22）、密码M=（2．67—2．9）（D／mm）时，此计算值符合实验平均值（2．7）。当年龄A^＊=（3，6）岁的屈光度变化已知时，我们计算其MOS预测年龄为A^＊=（7．3，21．8）岁（在不同条件下）。此值反比于M值在A=6及A=3的比值或N=N—N^＊，即非正视态及正视态的眼轴成长率之差。本理论也可用来预测在年龄A=25时的近视度，分别为D=-14及-0．49的上述两例情况，同时也能分析Lain等人的测量值（由出生到青年期的视力发展情况）。结论本理论可预测MOS、其后发展情况及其符合实验值（M）。使用成长率差值（dN）比使用L/rl比值能更准确地预测MOS。     

Early DAT is distinguished from aging by high-dimensional mapping of the hippocampus. Dementia of the Alzheimer type

OBJECTIVE: To determine the feasibility of using high-dimensional brain mapping (HDBM) to assess the structure of the hippocampus in older human subjects, and to compare measurements of hippocampal volume and shape in subjects with early dementia of the Alzheimer type (DAT) and in healthy elderly and younger control subjects. BACKGROUND: HDBM represents the typical structures of the brain via the construction of templates and addresses their variability by probabilistic transformations applied to the templates. Local application of the transformations throughout the brain (i.e., high dimensionality) makes HDBM especially valuable for defining subtle deformities in brain structures such as the hippocampus. METHODS: MR scans were obtained in 18 subjects with very mild DAT, 18 healthy elderly subjects, and 15 healthy younger subjects. HDBM was used to obtain estimates of left and right hippocampal volume and eigenvectors that represented the principal dimensions of hippocampal shape differences among the subject groups. RESULTS: Hippocampal volume loss and shape deformities observed in subjects with DAT distinguished them from both elderly and younger control subjects. The pattern of hippocampal deformities in subjects with DAT was largely symmetric and suggested damage to the CA1 hippocampal subfield. Hippocampal shape changes were also observed in healthy elderly subjects, which distinguished them from healthy younger subjects. These shape changes occurred in a pattern distinct from the pattern seen in DAT and were not associated with substantial volume loss. CONCLUSIONS: Assessments of hippocampal volume and shape derived from HDBM may be useful in distinguishing early DAT from healthy aging.     

MR spectroscopy study of dichloroacetate treatment after ischemic stroke

In a double-blind, placebo-controlled study, we used 1H MR spectroscopy to assess the effect of a single infusion of sodium dichloroacetate on lesion lactate 1 to 5 days after ischemic stroke. Apparent trends toward a reduction in lactate/N-acetyl compound ratios were seen at the higher drug doses employed, and in patients treated in the first 2 days following infarction. Use of spectroscopic measures as endpoints is feasible in acute stroke clinical trials.     

Misleading results with the 14-3-3 assay for the diagnosis of Creutzfeldt-Jakob disease

The definitive diagnosis of Creutzfeldt-Jakob disease (CJD) requires brain tissue analysis. A positive assay for the 14-3-3 protein in CSF has been suggested to be highly sensitive and specific in patients with CJD. The authors describe three patients for whom CSF 14-3-3 assays were falsely positive or falsely negative. Caution against overreliance on this putative biomarker is suggested in the diagnosis of CJD.     

Differentiation of atypical parkinsonian syndromes with routine MRI

OBJECTIVE: To evaluate the use of routine MRI in differentiating between patients with progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD) and control subjects. METHODS: Two neuroradiologists rated blindly and independently axial T2-weighted and proton density MR images of 54 patients with MSA, 35 patients with PSP, 5 patients with CBD, and 44 control subjects. RESULTS: More than 70% of patients with PSP and more than 80% of patients with cerebellar predominant MSA could be classified correctly with 0.5-T or 1.5-T scans, and no patient in these groups was misclassified. In the remaining patients an unequivocal differentiation could not be made. However, only approximately 50% of patients with parkinsonism-predominant MSA could be classified correctly, and 19% of them (all of whom had had 0.5-T scans) were misclassified. CONCLUSIONS: Characteristic findings on routine MRI, either 1.5 T or 0.5 T, can contribute to the identification of MSA and PSP. However, in a minority of patients no unequivocal diagnosis can be made using MRI findings alone.     

Preclinical characterization of AEG35156/GEM 640, a second-generation antisense oligonucleotide targeting X-linked inhibitor of apoptosis.

PURPOSE: Cancer cells can use X-linked inhibitor of apoptosis (XIAP) to evade apoptotic cues, including chemotherapy. The antitumor potential of AEG35156, a novel second-generation antisense oligonucleotide directed toward XIAP, was assessed in human cancer models when given as a single agent and in combination with clinically relevant chemotherapeutics. EXPERIMENTAL DESIGN: AEG35156 was characterized for its ability to cause dose-dependent reductions of XIAP mRNA and protein in vitro and in vivo, to sensitize cancer cell lines to death stimuli, and to exhibit antitumor activity in multiple human cancer xenograft models as a single agent or in combination with chemotherapy. RESULTS: AEG35156 reduced XIAP mRNA levels with an EC50 of 8 to 32 nmol/L and decreased XIAP protein levels by >80%. Loss of XIAP protein correlated with increased sensitization to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in Panc-1 pancreatic carcinoma cells. AEG35156 exhibited potent antitumor activity relative to control oligonucleotides in three human cancer xenograft models (prostate, colon, and lung) and was capable of inducing complete tumor regression when combined with taxanes. Antitumor effects of AEG35156 correlated with suppression of tumor XIAP levels. CONCLUSIONS: AEG35156 reduces XIAP levels and sensitizes tumors to chemotherapy. AEG35156 is presently under clinical assessment in multiple phase I trials in cancer patients as a single agent and in combination with docetaxel in solid tumors or cytarabine/idarubicin in leukemia.     

Magnetic resonance imaging of growth plate injuries: the efficacy and indications for surgical procedures

In 23 patients with growth plate injuries, magnetic resonance imaging (MRI) studies were performed a total of 31 times to evaluate the physis which showed plain radiographic evidence of possible damage. Fourteen patients clinically showed growth arrest, and 10 patients required a Langenskiold operation. In 3 patients who underwent this operation, subsequent premature total fusion of the physis adversely affected the postoperative results. We propose that the merging shape of the arrest line with calcification of the provisional zone of the metaphysis shown by MRI indicates poor viability of the physis. MRI provided useful information on the appearance of the growth plate and changes in the metaphysis, both of which affected the prognosis and the results of the surgical procedures.