Neuroblastoma Originating from Extra-abdominal Sites: Association with Favorable Clinical and Biological Features

Neuroblastomas originating from different sites might have different clinical and biological characteristics. In the present study, the clinical (age, sex and stage) and biological (N-myc amplification, Shimada pathology and levels of lactate dehydrogenase, ferritin and neuron-specific enolase) characteristics of patients with newly diagnosed neuroblastoma were compared according to the site of tumor origin (extra-abdominal versus abdominal). The event-free survival rate (EFS) was also compared between the two groups. Among 143 neuroblastomas, 115 tumors originated from the abdomen, 26 from extra-abdominal sites and 2 from unknown primary sites. Frequencies of stage 4 tumor and N-myc amplified tumor were lower in the extra-abdominal group than in the abdominal group (34.6% vs. 60.0%, P=0.019 and 4.2% vs. 45.0%, P<0.001, respectively). Levels of lactate dehydrogenase, ferritin and neuron-specific enolase were significantly lower in the extra-abdominal group than in the abdominal group. The probability of 5-yr EFS (±95% confidence interval) was higher in the extra-abdominal group than in the abdominal group (94.4±10.6% vs. 69.4±9.4%, P=0.026). Taken together, neuroblastomas originating from extra-abdominal sites might be associated with more favorable clinical and biological characteristics and a better outcome than neuroblastomas originating from abdomen.     

Mechanism of infarction involving ipsilateral carotid and posterior cerebral artery territories

BACKGROUNDS: We investigated the potential mechanism of infarction involving the territories of both the internal carotid artery (ICA) and the ipsilateral posterior cerebral artery (PCA). METHODS: Among consecutive patients with an ischemic stroke who had undergone both diffusion-weighted magnetic resonance imaging (DWI) and cerebral angiography, those who were found to have acute lesions in the ipsilateral ICA and PCA territories on DWI were selected for this study. The mechanism of infarction was sought by investigating angiographic findings and DWI lesion patterns. The frequency of patency between the ICA and PCA in the patient group was compared with that in the normal control group. RESULTS: Infarctions involving ipsilateral ICA and PCA territories were rare (21 of 1,388 patients, 1.5%). Sixteen of those 21 patients (76%) demonstrated steno-occlusive lesions of the relevant ICA. Cardioembolic sources were rarely found. All but 1 patient with fetal-type PCA (fPCA) or the posterior communicating artery demonstrated significant ICA stenosis. The fPCA was more frequently found in the ipsilateral hemisphere of patients with an infarction than in the control group (44.4 vs. 18.5%, p = 0.006). Ischemic lesions in the ICA territory were usually small but multiple, and those in the PCA territory were single and located in the cortex. CONCLUSIONS: Large artery atherosclerosis of the carotid artery was very common in patients with infarctions involving the ipsilateral ICA and PCA territories. Extracranial cervical artery evaluation is indispensable in those patients.     

Improved time intervals by implementation of computerized physician order entry-based stroke team approach

BACKGROUND: The need for rapid evaluation and treatment of acute stroke patients has been well documented. A computerized physician order entry (CPOE) system can improve communication and provide immediate access to information, which may be useful for an effective team approach program targeted to reduce in-hospital time delays. METHODS: To reduce the time from a patient's arrival at the emergency department to thrombolysis, a team approach program using CPOE was developed, and its efficacy was investigated by comparing time intervals from arrival to evaluation and intravenous tissue-type plasminogen activator (tPA) treatment before and after the implementation of the program. RESULTS: Among 379 consecutive patients who were screened as potential candidates for thrombolysis, 25 patients (6.6%) received tPA during a 1-year period after initiation of the program. Fourteen patients were treated with tPA in the previous year. After program implementation, time from arrival to computed tomography scan was reduced from 34 to 19 min (p = 0.01). Time to report of complete blood count was also shortened from 52 to 33 min (p < 0.01). Finally, time from arrival to tPA treatment was reduced by 23 min (from 79 to 56 min; p < 0.01). Onset-to-door time tended to be longer after the program implementation (from 41 to 60 min; p = 0.14). CONCLUSIONS: Implementation of the CPOE-based team approach program significantly reduced time from emergency department arrival to evaluations and treatment.     

A simple method to estimate cardiac function during routine multi-row detector CT exams

Cardiac dysfunction may be suggested at computed tomography (CT) exams by the presence of morphological abnormalities such as cardiac enlargement and thickening of the pulmonary interlobular septa. However, these morphological signs are non specific. We evaluated whether right-to-left cardiac transit time of contrast during single-level timing scans could predict the cardiac output and ejection fraction. In a consecutive group of 100 patients referred for body CT, a preliminary single-level study was used to measure the right-to-left ventricular transit time of intravenously injected contrast medium. In all these patients, the cardiac index (cardiac output corrected for body surface area, CI) and ejection fraction (EF) were calculated using cardiac magnetic resonance imaging (CMR). Data of the first half (50 patients, group A) were used to establish a method and concept to predict the cardiac index and ejection fraction with CT. The method was validated in the next half (50 patients, group B) by comparing the predicted CT results with those obtained with CMR. There was a good correlation of the observed CI with CMR and observed transit time on CT in group B (P < 0.05; R² 0.70 ). Functional CT estimates of CI and EF in group B correlated well with the CMR results for CI and EF (P < 0.05; R² 0.66 for CI and P < 0.05; R² 0.49 for EF). The presence of a right-to-left ventricular transit time of more than 10.5 s indicated cardiac dysfunction with a specificity and positive predictive value of 100%. Right-to-left transit time obtained during routine body CT exams can provide valuable physiological information on global cardiac function.     

Assessment of Lymph Node Metastases by Contrast-Enhanced MR Imaging in a Head and Neck Cancer Model

Objective

We wanted to investigate the accuracy of contrast-enhanced MR imaging for the detection of lymph node metastases in a head and neck cancer rabbit model.

Materials and Methods

The metastatic lymph node model we used was created by inoculating VX2 tumors into the auricles of six New Zealand White rabbits. T1-weighted MR images were obtained before and after injecting gadopentetate dimeglumine at three weeks after tumor cell inoculation. The sizes, signal intensity ratios (i.e., the postcontrast signal intensities of the affected nodes relative to the adjacent muscle) and the enhancement patterns of 36 regional lymph nodes (parotid and caudal mandibular nodes) were evaluated on MR images and then compared with the histopathologic findings.

Results

No statistical difference was found between the sizes of 12 metastatic (10.5±3.2 mm) and 24 hyperplastic (8.0±3.6 mm) lymph nodes (p > 0.05). On the contrast-enhanced T1-weighted MR images, nine metastatic and four hyperplastic lymph nodes had peripheral high and central low signal intensity, whereas three metastatic and 20 hyperplastic lymph nodes had homogeneous high signal intensity. Using a signal intensity ratio less than one as a diagnostic criterion for a metastatic lymph node, the sensitivity, specificity and positive and negative predictive values of the enhanced MR images were 75% (9/12), 83% (20/24), 69% (9/13) and 87% (20/23), respectively, with areas under receiver-operating-characteristic curve values of 0.81.

Conclusion

This experimental study confirms that metastatic and hyperplastic lymph nodes can be differentiated using MR images on the basis of the contrast uptake patterns, but that they cannot be differentiated using any particular size criteria.     

Domain structure of the DEMETER 5-methylcytosine DNA glycosylase

DNA glycosylases initiate the base excision repair (BER) pathway by excising damaged, mismatched, or otherwise modified bases. Animals and plants independently evolved active BER-dependent DNA demethylation mechanisms important for epigenetic reprogramming. One such DNA demethylation mechanism is uniquely initiated in plants by DEMETER (DME)-class DNA glycosylases. Arabidopsis DME family glycosylases contain a conserved helix-hairpin-helix domain present in both prokaryotic and eukaryotic DNA glycosylases as well as two domains A and B of unknown function that are unique to this family. Here, we employed a mutagenesis approach to screen for DME residues critical for DNA glycosylase activity. This analysis revealed that amino acids clustered in all three domains, but not in the intervening variable regions, are required for in vitro 5-methylcytosine excision activity. Amino acids in domain A were found to be required for nonspecific DNA binding, a prerequisite for 5-methylcytosine excision. In addition, mutational analysis confirmed the importance of the iron-sulfur cluster motif to base excision activity. Thus, the DME DNA glycosylase has a unique structure composed of three essential domains that all function in 5-methylcytosine excision.     

Introduction of the Electrical Next Generation Impactor (eNGI) and Investigation of its Capabilities for the Study of Pressurized Metered Dose Inhalers

Purpose

To introduce the design of the electrical Next Generation Impactor (eNGI), and validate its proposed function as a method of electrostatic characterization for pressurized metered dose inhaler (pMDI) formulations.

Methods

Flixotide® (fluticasone propionate), Ventolin® (salbutamol sulphate), and QVAR® (beclomethasone dipropionate) were used as model pMDIs in this study. At an airflow rate of 30 l/min, five individual actuations of each pMDI were introduced into the electrical low-pressure impactor (ELPI), Next Generation Impactor (NGI), and the eNGI. Charge profiles for each actuation were measured by the ELPI and eNGI, while mass profiles were recorded by the all three impactors.

Results

The difference in estimated mass median aerodynamic diameters and geometric standard deviations for all pMDIs using the NGI and eNGI were not found to be statistically significant (p?     

The needs of people with dementia in care homes: the perspectives of users, staff and family caregivers

ABSTRACTBackground: People with dementia in care homes are at risk of having their views ignored and decisions are often made on their behalf by care home staff and family carers. The aim of this study was to compare the ratings of needs of older people with dementia living in care homes, as assessed by the older person themselves, a family caregiver, and the staff of the care home.Method: The Camberwell Assessment of Need for the Elderly (CANE) was completed for 238 residents with dementia by care staff. In addition, 149 users and 81 family caregivers also completed the assessment of the person's met and unmet needs.Results: Many users were able to report their met and unmet needs despite having moderately severe dementia. The views of the person with dementia were commonly in agreement with the staff and family carers' views. However, user and carer pairs had the lowest average percentage agreement of 63% compared to that of 77% between user and staff pairs. In particular, users reported relatively higher unmet needs for psychological distress, company and information, and high unmet needs for daytime activities and eyesight/hearing problems.Conclusions: Users' views on their needs should be sought even when the person has dementia and lives in a care home. Reliance solely on assessment by staff or carers may lead to under recognition of unmet needs.     

Chronic cerebral hypoperfusion protects against acute focal ischemia, improves motor function, and results in vascular remodeling

Atherosclerosis may cause severe stenosis of the arteries supplying the brain, which induces chronic cerebral hypoperfusion. Although an infarction often occurs in this area, it is uncertain how brain vessels respond to the chronic hypoperfusion or how the vascular responses are related to stroke severity when the area has been subjected to severe ischemia. To address these uncertainties, we induced chronic cerebral hypoperfusion in Sprague-Dawley rats with a bilateral common carotid artery ligation (BCAL). A middle cerebral artery occlusion/reperfusion (MCAO/R) was introduced with a nylon suture four weeks after either BCAL (BCAL-MCAO) or a sham operation (Sham-MCAO). Motor disability scores and infarct sizes, based on 2,3,5-triphenyltetrazolium chloride staining, were significantly reduced with BCAL-MCAO treatment compared with sham-MCAO treatment (P<0.01). The diameters of the posterior cerebral, posterior communicating, and basilar arteries on the brain surface were larger and more tortuous in BCAL-treated rats (P<0.01). The density of large capillary- and arteriole-sized vessels in the brain parenchyma also increased in BCAL-treated rats (P<0.05). Strokes were less severe when the vicinity subjected to infarction was preconditioned with chronic cerebral hypoperfusion. Increasing the vascular reserve with adaptive vascular remodeling may have contributed to this response.