Alterations in Acrolein Metabolism Contribute to Alzheimer's Disease.

Alzheimer's disease (AD) is a detrimental neurodegenerative disease, and early diagnosis appears to be the key to successful treatment. Acrolein, a byproduct of lipid peroxidation, has been shown to contribute to the pathological process of AD. This study recruited 118 elderly subjects consisting of 58 non-demented control subjects and 62 AD patients. We analyzed the acrolein-related metabolites in the plasma, cerebrospinal fluid (CSF), and urine of all subjects. We found that the levels of acrolein-conjugated protein (Acr-PC) in the plasma (p = 0.00012) and CSF (p = 0.00161) of AD patients were significantly higher than those of control subjects, whereas the levels of a urinary acrolein metabolite, 3-hydroxypropyl mercapturic acid (3-HPMA), were markedly decreased (p = 0.00882) in AD patients. These data suggest that deregulated acrolein metabolism may be correlated with neuronal damage in AD patients, which might provide further insights into the disease progression and early diagnosis of AD.

Patterns of outpatient care utilization by seniors under the National Health Insurance in Taiwan.

BACKGROUND/PURPOSE: Taiwan has one of the fastest growing aging populations in the world, which makes the effective allocation of scarce medical resources a key issue. This paper investigates patterns in the use of outpatient services by elderly individuals in Taiwan under the National Health Insurance (NHI) program. METHODS: We assembled a random sample from the NHI Research Database in Taiwan, comprising 50% of all claims made for elderly people (65 years old) in 2010 (n 1,239,836 beneficiaries) including 14 variables. RESULTS: In 2010, individuals aged 65 years or older comprised 10.74% of the population of Taiwan, and accounted for 11.39% of all physician and outpatient visits. The rate of medical care visits was 28.54 ± 21.23 (Standard deviation) times per person per annum, with a higher rate for women, those in the 80-84 age group, low-income beneficiaries, and the inhabitants of offshore islands. The three most frequent diagnoses for elderly patients were hypertension, diabetes, and acute upper respiratory infections. The mean insured medical costs per person per annum were US Dollars 1,132, with higher expenses for men, those in the 80-84 age group, and those inhabiting urban areas. CONCLUSION: This study employed nationally representative data in the detection of patterns in outpatient care utilization by elderly individuals in Taiwan. Medical care providers and policymakers should be fully aware of the complex patterns unique to older patients. The results of this study could be used as a benchmark with which to assess the impact of future medical care policy on elderly people.

A diagnostic methodology for Alzheimer's disease.

BACKGROUND: Like all other neurodegenerative diseases, Alzheimer's disease (AD) remains a very challenging and difficult problem for diagnosis and therapy. For many years, only historical, behavioral and psychiatric measures have been available to AD cases. Recently, a definitive diagnostic framework, using biomarkers and imaging, has been proposed. In this paper, we propose a promising diagnostic methodology for the framework. METHODS: In a previous paper, we developed an efficient SVM (Support Vector Machine) based method, which we have now applied to discover important biomarkers and target networks which provide strategies for AD therapy. RESULTS: The methodology selects a number of blood-based biomarkers (fewer than 10% of initial numbers on three AD datasets from NCBI), and the results are statistically verified by cross-validation. The resulting SVM is a classifier of AD vs. normal subjects. We construct target networks of AD based on MI (mutual information). In addition, a hierarchical clustering is applied on the initial data and clustered genes are visualized in a heatmap. The proposed method also performs gender analysis by classifying subjects based on gender. CONCLUSIONS: Unlike other traditional statistical analyses, our method uses a machine learning-based algorithm. Our method selects a small set of important biomarkers for AD, differentiates noisy (irrelevant) from relevant biomarkers and also provides the target networks of the selected biomarkers, which will be useful for diagnosis and therapeutic design. Finally, based on the gender analysis, we observe that gender could play a role in AD diagnosis.

The association of geographical location and neighbourhood deprivation with older people's use of NHS Direct: a population-based study.

BACKGROUND: no research has investigated how older people's use of NHS Direct, the 24-h telephone health advice and information service in England and Wales, varies according to geographical location and deprivation. OBJECTIVES: to describe the geographic pattern of older people's use of NHS Direct and examine the relationship between service use and deprivation. DESIGN: descriptive, exploratory, cross-sectional, population-based study. SETTING: calls to all 32-NHS Direct contact centres in England/Wales. PARTICIPANTS: people aged 65 years and above who used NHS Direct between 1 December 2007 and 30 November 2008. RESULTS: differences in older people's use of NHS Direct were observed in England and Wales. In England, the call rate was highest in Yorkshire and the Humber and was lowest in the West Midlands. At the postcode level, the rate of calls ranged from 0.167 (Blackburn) to 0.011 (Carlisle) per person per annum. In England, but not in Wales, the level of deprivation was associated with the rate of calls, older people living in the most deprived areas had the highest rate of calls to NHS Direct. CONCLUSIONS: the results are useful for future planning to meet the needs of older people, and in informing national policies for the development of NHS Direct.

Cancer classification: Mutual information, target network and strategies of therapy.

BACKGROUND: Cancer therapy is a challenging research area because side effects often occur in chemo and radiation therapy. We intend to study a multi-targets and multi-components design that will provide synergistic results to improve efficiency of cancer therapy. METHODS: We have developed a general methodology, AMFES (Adaptive Multiple FEature Selection), for ranking and selecting important cancer biomarkers based on SVM (Support Vector Machine) classification. In particular, we exemplify this method by three datasets: a prostate cancer (three stages), a breast cancer (four subtypes), and another prostate cancer (normal vs. cancerous). Moreover, we have computed the target networks of these biomarkers as the signatures of the cancers with additional information (mutual information between biomarkers of the network). Then, we proposed a robust framework for synergistic therapy design approach which includes varies existing mechanisms. RESULTS: These methodologies were applied to three GEO datasets: GSE18655 (three prostate stages), GSE19536 (4 subtypes breast cancers) and GSE21036 (prostate cancer cells and normal cells) shown in. We selected 96 biomarkers for first prostate cancer dataset (three prostate stages), 72 for breast cancer (luminal A vs. luminal B), 68 for breast cancer (basal-like vs. normal-like), and 22 for another prostate cancer (cancerous vs. normal. In addition, we obtained statistically significant results of mutual information, which demonstrate that the dependencies among these biomarkers can be positive or negative. CONCLUSIONS: We proposed an efficient feature ranking and selection scheme, AMFES, to select an important subset from a large number of features for any cancer dataset. Thus, we obtained the signatures of these cancers by building their target networks. Finally, we proposed a robust framework of synergistic therapy for cancer patients. Our framework is not only supported by real GEO datasets but also aim to a multi-targets/multi-components drug design tool, which improves the traditional single target/single component analysis methods. This framework builds a computational foundation which can provide a clear classification of cancers and lead to an efficient cancer therapy.

Older people's use of NHS Direct.

INTRODUCTION: the 24 h telephone health information and advice service in England and Wales, NHS Direct, aims to help callers manage health problems and relieve pressure on primary healthcare services. Although older people may use NHS Direct less than other age groups, no research has specifically investigated older people's use of the service. AIMS: the aim of this study was to describe the older people's use of NHS Direct and to explore differences in the use of NHS Direct among subgroups of older people. METHODS: a cross-sectional exploratory descriptive design utilising quantitative methods was adopted. Data on all calls made to NHS Direct by, or on behalf of, people aged 65 and over between 1 December 2007 and 30 November 2008 were analysed. RESULTS: a total of 402,959 telephone calls were made to NHS-Direct regarding older people during the 12-month study period. The call rate was higher among women and in older age groups. Most calls were regarding actual symptoms, e.g. pain, digestive problems. CONCLUSIONS: this research identifies the characteristics of calls made to NHS Direct relating to older people and how they use the service. This will help with the planning and development of services to meet the needs of the older population.

Development of a patient-oriented tool for evaluating the quality of breast cancer information on the internet.

The aim of this study was to develop a tool for evaluating the quality of breast cancer information on the Internet from the perspective of patients and their families. A specific tool, Breast Cancer tool (BC tool), was developed based on the information needs of women with breast cancer and their families reported in the literature. The BC tool and other 3 generic tools (HON, IQ tool, Discern) were used to assess 40 breast cancer websites. The reliability and validity of each tool was examined and the time spent reviewing the websites was measured. The four tools were shown to have acceptable reliability (Cronbach's alpha>0.7), convergent validity, especially the BC tool which was capable of distinguishing whether a website offers sufficient information for women and their families. However, the BC tool took more time than the other tools to use, suggesting relatively low feasibility. The results of this study reinforce the importance of developing specific tools from perspectives of patients and their family members.

Hypertension-induced cerebellar encephalopathy and hydrocephalus in a male.

Hypertensive encephalopathy is believed to be caused by an abrupt elevation in systemic blood pressure. It rarely occurs in children and can be neurologically devastating if it is not recognized and treated immediately. This report describes an 11-year-old male who presented with edema and a cerebellar lesion, with acute obstructive hydrocephalus resulting from hypertensive encephalopathy. A shunt was inserted to relieve pressure in the acute stage. The patient's hydrocephalus and cerebellar swelling subsided when his blood pressure was controlled. The cerebellar lesion had been initially diagnosed as a glioma. In children, a cerebellar lesion occurring with acute obstructive hydrocephalus and hypertensive encephalopathy is rare but reversible. Clinicians should be aware of this condition because it might be misdiagnosed as a tumor of the posterior fossa.

Right ventricular dysfunction secondary to acute massive pulmonary embolism detected by helical computed tomography pulmonary angiography.

OBJECTIVE: Acute massive pulmonary embolism causes abrupt pulmonary arterial hypertension and right ventricular dysfunction (RVD). Patients with RVD have a worse prognosis than those with normal right ventricular function. Consequently, recognizing the RVD at the time of pulmonary embolism is useful for risk stratification and enables more aggressive therapy. The study compared the accuracy of helical computed tomographic (CT) scans with echocardiography in the detecting of RVD in patients with acute massive pulmonary embolism. MATERIALS AND METHODS: Specifically, this work reviewed the CT pulmonary angiograms of 14 patients who were positive for acute massive pulmonary embolism during a 52-month period. CT scans were reviewed for findings indicating RVD. Scans were considered positive for RVD if the right ventricle was dilated or there was leftward shift of the interventricular septum. Echocardiographic reports serving as the reference standard for the diagnosis of RVD were also reviewed. CT study results were then correlated with echocardiography results. RESULTS: Among 14 patients with massive pulmonary embolism, echocardiography identified 12 patients having RVD, whereas the remaining two patients were negative for RVD. Meanwhile, CT correctly identified 11 of 12 patients as having RVD, and was negative for RVD in the remaining 3 patients. Correlated with echocardiography, CT scan for RVD detection had a sensitivity of 91.6% and a specificity of 100%. CONCLUSIONS: CT can accurately detect RVD in patients with acute massive pulmonary embolism. However, this result requires confirmation using a larger prospective cohort study.

Inadvertent embolization of a persistent sciatic artery in pelvis trauma.

We describe a case of unilateral persistent sciatic artery (PSA), a rare vascular anomaly, in a 43-year-old woman with severe multiple trauma. A small amount of diluted embolization particles went into this vessel during emergent endovascular therapy under fluoroscopic monitoring. The procedure was immediately stopped when the true nature of the anatomic variant was recognized. Fortunately, an ischemic event of the lower leg did not occur. The imaging findings of computed tomography and digital subtraction angiography are presented and the relevant literature is reviewed.

Proton magnetic resonance spectroscopic imaging of cerebral gliomas: correlation of metabolite ratios with histopathologic grading.

BACKGROUND: Magnetic resonance spectroscopic imaging (MRSI) can provide spatially encoded metabolite information and improve tissue specificity in human brains. The major goal of this study was to evaluate the correlation of metabolite ratios measured by MRSI with histopathological grading of cerebral gliomas. METHODS: Twenty-seven patients with cerebral gliomas were referred consecutively for pre-surgical evaluation. The lesions included 10 grade II, 5 grade III, and 12 grade IV gliomas. MRSI data were acquired during the same session of conventional magnetic resonance imaging and analyzed in terms of N-acetylaspartate (NAA), creatine-phosphocreatine (Cr), choline-containing compounds (Cho), and lactate. RESULTS: There were significantly lower NAA/Cr and higher Cho/Cr, Cho/NAA and (Cho+Cr)/NAA ratios (ps < 0.001) in gliomas than in normal tissues. There were significantly lower NAA/Cr and higher Cho/NAA and (Cho+Cr)/NAA ratios (ps < or = 0.05) in World Health Organization (WHO) grade III or IV gliomas than in grade II gliomas. A significant correlation was identified between the (Cho+Cr)/NAA ratio and WHO grade (p < 0.05). There was no significant metabolite difference between grade III and grade IV tumors (ps > 0.1), or significant difference in lactate occurrence rates among different grades (p = 0.26). CONCLUSIONS: Proton MRSI can provide in vivo information about the metabolic status of cerebral gliomas, and the (Cho+Cr)/NAA ratio can discriminate different grades better than other metabolite ratios. However, substantial overlap of metabolite ratios among different severities of malignancy makes it impossible to confirm the WHO grade of a specific cerebral glioma by using clinical MRSI.

Experience in the surgical management of spontaneous spinal epidural hematoma.

OBJECT: Spontaneous spinal epidural hematoma (SSEH) is a rare disease entity. Although many cases have been reported in the literature, controversy persists as to its origin, diagnosis, and timing of treatment. The authors conducted a study in patients treated in their hospital and report the results. METHODS: Clinical data obtained in 35 patients with SSEH were retrospectively reviewed. Age, sex, history of hypertension, and history of anticoagulation therapy were recorded, and data were analyzed to clarify the possible predisposing factors of SSEH. Neurological outcomes were reappraised using a standardized grading system and correlated with the time interval from initial ictus to surgery, duration of complete neurological deficits, and the rapidity of deterioration of paralysis. Nonparametric methods and Spearman rank-correlation coefficients were used for statistical analysis. CONCLUSIONS: Surgery is a safe and effective procedure to treat SSEH. The disease-related mortality rate was 5.7%, the surgery-related complication rate was 2.9%, and there were no operation-related deaths. Neurological outcome after surgery is positively correlated with preoperative neurological deficits (88.9% complete recovery in patients with incomplete neurological deficits compared with 37.5% in those with complete deficits [p < 0.001]). In patients in whom the time interval from initial ictus was shorter (< 48 hours) and in whom the duration of complete neurological symptoms was also briefer (< 12 hours), there is a positive correlation with better neurological and functional recovery (p < 0.05).