Investigation of the motor system in two siblings with Canavan's disease: a combined transcranial magnetic stimulation (TMS) - diffusion tensor imaging (DTI) study.

Canavan's disease (CD) is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene (ASPA), leading to spongiform degeneration of the white matter and severe impairment of psychomotor development. We present the cases of two non-Jewish sisters with CD that have a milder and protracted clinical course compared to typical CD. MRI imaging revealed bilateral high-signal-intensity areas in the thalami and the internal capsule and MR spectroscopy showed typical findings for CD (a marked increase in N-acetylaspartate (NAA) levels). FA values of the right and left corticospinal tracts at the level of the posterior limb of the internal capsule, and the centrum semiovale were found to be significantly reduced compared to healthy controls. From a neurophysiological point of view, the peripheral motor system was normal. In contrast, cortical stimulation at maximal intensity failed to elicit facilitated or resting MEPs and silent periods (SPs) in upper and lower limbs, providing evidence for significant upper motor pathway dysfunction.

The role of cytokines in pulp inflammation.

Pulpitis is a typical inflammatory disease of dental pulp, characterized by the local accumulation of inflammatory mediators, including cytokines and chemokines. In addition to serving as intercellular messengers mediating the inflammatory response, cytokines and chemokines induce the expression and stimulate the activity of molecular and cellular agents which participate actively in destructive and reparative processes in the pulp. It is the balance between these processes which eventually determines the extent of pulp inflammation and the viability of the affected tooth. Over the last decade, a number of studies have attempted to correlate cytokine gene expression in the pulp with various stages of inflammation, with possible diagnostic applications in mind. A small survey of relevant information is presented in this paper.

The role of P53 and Bcl-2 proteins in 7, 12-dimethylbenz-(a)-anthracene-induced tumor growth.

7, 12- Dimethylbenz-(a)-anthracene (DMBA) has been used for a long time to induce rat mammary gland carcinogenesis. In a previous paper we described the effects of diet, of non-steroidal anti-inflammatory drugs and the combination of these two factors on breast cancer. We also pointed out that DMBA tumor generating process is still poorly understood. The present study attempts to explore whether P53 or the pro-apoptotic protein Bcl-2 are potential targets of DMBA in its induction of breast tumors in the Sprague-Dawley rat breast tumorigenesis model. Our results indicate that the DBMA-induced tumors are apparently the result of P53 inactivation. This inactivation results in tumorigenesis, probably aided by the absence of Bcl-2 in the tumor cells of the Sprague-Dawley rat animal model. We discuss the potential mechanisms by which P53 inactivation results in tumorigenesis.

A semi-automated approach towards generating three-dimensional mesh of the heart using a hybrid MRI/histology database.

Both the forward and inverse problems of electrocardiography rely on the precise modelling of the anatomic and electrical properties of the thoracic tissues. This, in turn, requires good knowledge of the electrical anisotropy as well as conductivity inhomogeneity of the heart, lungs and the rest of the thorax. Cardiac electrical anisotropy is related to its microstructure (fibre length, density and orientation). We hereby present detailed three-dimensional (3D) meshes of the thorax and heart, using image data from contiguous 2D magnetic resonance (MR) imaging slices as well as a realistic 3D cardiac fibre orientation model that derives its data from high-resolution ex vivo human heart MR images and from histology specimens of heart tissue. Using specific software, we integrated the 3D thorax and heart meshes in one that addresses the related modelling requirements for the solution of the forward and inverse problems of electrocardiography.

Cognitive event-related potentials: longitudinal changes in mild cognitive impairment.

OBJECTIVE: To measure changes over time in the latency and amplitude of the major waves of auditory event-related potentials (AERP) and their correlation with the memory status of patients with mild cognitive impairment (MCI). METHODS: AERPs were recorded in 22 MCI patients (mean±SD age=67.4±7.8, median (interquartile range-IQR) MMSE score=28 (27-29) in three consecutive exams and in 30 age-matched controls at baseline. During this time period, 3 patients converted to Alzheimer disease (AD). Latencies and amplitudes of N200, P300 and Slow Wave and the N200-P300 peak-to-peak amplitudes and latencies were determined, and correlation coefficients (CC) between them and MMSE scores were calculated. RESULTS: A significant increase in the P300 latency and a decrease in the N200 amplitude were observed between the exams. Only N200 latency correlated with baseline MMSE scores, whereas P300 and Slow Wave latencies correlated with age. CONCLUSIONS: N200 amplitude is more sensitive in identifying differences over time at the early stages of the disease, whereas P300 latency at later stages. SIGNIFICANCE: A new N2-P3 inter-peak index that incorporates changes in N200 and P300 latencies and amplitudes into a single parameter is introduced in order to adequately describe the gradual progress of MCI and its transition to AD.

Consensus statement on dementia education and training in Europe.

OBJECTIVES: The aim of the current statement is to agree on: (1) what is the current situation with education and training on dementia in Europe; (2) what are the minimum educational requirements for professionals (neurologists, psychiatrists, primary care providers, nurses, biologists, neuroradiologists, etc.) regarding Alzheimer's disease and dementia, and (3) how to start a course of action for the future. DESIGN: In 2005, a simple questionnaire was sent to members of the European Alzheimer's Disease Consortium (EADC) concerning the education and training on dementia in their countries. Fourteen universities of the respective countries responded to this simple questionnaire. The answers varied, and the conclusion of this effort was that little was done concerning the training of students and health professionals on dementia. In 2008, another more structured and specified questionnaire was sent to professors in different universities of the same countries. RESULTS: The answers obtained were different from those of the previous questionnaire and demonstrated that it is very difficult to know about training and education in the field of dementia in every European country. CONCLUSION: From the data collected, it seems that although in the recent past little had been done concerning training on dementia, nowadays training has been developed in most European countries, and relevant educational projects exist both for medical students and doctors during their specialty training. Our main purpose is to develop training material or develop specific courses to improve the professional knowledge about dementia so that best medical and non-medical practice is implemented.

Combination of P300 and CSF ß-amyloid(1-42) assays may provide a potential tool in the early diagnosis of Alzheimer's disease.

BACKGROUND/AIMS: The aim of this study was to investigate the diagnostic role of CSF beta amyloid(1-42) levels and auditory event-related potentials (AERPs) in the progression of mild cognitive impairment (MCI) to Alzheimer's disease (AD). METHODS: In fifty three MCI patients a lumbar puncture was performed and beta amyloid(1-42) levels were determined. Twenty patients were re-examined after 11 months. During this period five of them progressed to AD. Neuropsychological and ERP examinations were performed in all patients at both exams. RESULTS: Compared to MCI stable patients, AD-converters showed significantly lower beta-amyloid(1-42) values both for group 1 (Mann Whitney test, Z=-2.952, p=0.003, effect size r=-0.41) and group 2 (Z=-2.458, p=0.011; effect size r=-0.55). On the other hand, the patients of group 1 who converted to AD had prolonged latencies and lower amplitudes of the P300 wave compared to those of the MCI-stable patients, although the differences were not significant. CONCLUSIONS: Compared to the separate use of CSF beta-amyloid(1-42) and AERPs, higher values of sensitivity and specificity were achieved by the combined use of beta-amyloid(1-42) levels and P300 latencies (80% and 98%) or amplitudes (100% and 89%) in the discrimination between AD converters and MCI stable patients. Therefore the combination of an electrophysiological and a biological marker is potentially of high diagnostic value for the early diagnosis of AD converters.

Progression of mild cognitive impairment to Alzheimer's disease: improved diagnostic value of the combined use of N200 latency and beta-amyloid(1-42) levels.

BACKGROUND/AIMS: The aim of this study was to investigate the role of cerebrospinal fluid beta-amyloid(1-42) levels and auditory event-related potentials (AERPs) in the progress of mild cognitive impairment (MCI) to Alzheimer's disease (AD). METHODS: In 53 MCI patients, lumbar puncture was performed and beta-amyloid(1-42) levels were determined. Twenty patients were reexamined after 11 months. During this period, 5 of them progressed to AD. Neuropsychological and ERP analyses were performed on all patients during both baseline and endpoint examinations. RESULTS: Compared to stable MCI patients, those that progressed to AD had significantly lower beta-amyloid(1-42) levels (Mann-Whitney test, Z = -2.952, p = 0.003; effect size r = -0.41) and significantly prolonged N200 latencies (Mann-Whitney test, Z = -3.561, p < 0.001, effect size r = -0.49). From ERP variables, only the N200 latency significantly correlated with beta-amyloid(1-42) levels (baseline examination: r(s) = -0.421, p = 0.002; follow-up examination: r(s) = -0.574, p = 0.008). CONCLUSIONS: The combined use of these two parameters enabled discrimination of stable MCI patients from those who developed AD, with 100% sensitivity and specificity. Therefore, this method could be of high diagnostic value for the early diagnosis of AD.

Effects of rich-in-fat diets and highly selective COX-2 inhibitors on 7,12-dimethylbenz-(A)-anthracene-induced tumor growth.

The effects of diet, of non-steroidal anti-inflammatory drugs, or of their combination on carcinogenesis continue to be a case for controversy. Diets that are high in fat have been linked to increased risk of various tumors. At the same time there is substantial, but not conclusive, evidence that the risk of breast and colon cancer correlates with total fat intake rather than a specific type of fat. On the other hand, non-steroidal anti-inflammatory drugs (NSAIDs) have been studied extensively because they appear to delay or inhibit the development of malignant and pre-malignant lesions. 7,12-Dimethylbenz-(a)-anthracene (DMBA) has been used for a long time to induce carcinogenesis in a number of rat animal models. The present study attempts to identify the effects on DMBA-induced tumor growth (a) of diets rich in fat and (b) of the highly selective COX-2 inhibitor Celecoxib, which has been claimed to offer substantial protection against carcinogenesis.

Prediction of conversion from mild cognitive impairment to Alzheimer's disease by CSF cytochrome c levels and N200 latency.

The aim of the present study was to investigate the role of CSF cytochrome c levels and auditory event-related potentials (AERPs) on the progress of mild cognitive impairment (MCI) to Alzheimer's disease (AD). Fifty one patients diagnosed with MCI and fourteen healthy individuals underwent lumbar puncture at baseline and their CSF cytochrome c levels were determined. A follow-up examination of cytochrome c levels took place in 20 patients after 11 months and in this period five of the patients progressed to AD. ERP examinations were also performed in all patients both at baseline and follow-up. MCI patients had significantly higher cytochrome c levels compared to healthy controls (Mann-Whitney test, Z=-2.110, p=0.018). Compared to MCI patients who remained stable, the AD-converters, had a higher increase over time in cytochrome c levels (Mann-Whitney test, p=0.002; effect size r=0.63) and significantly prolonged N200 latency (Mann-Whitney test, p<0.001; effect size r=0.50). Amongst investigated ERP variables, only N200 amplitude was significantly correlated with CSF cytochrome c levels (rs=0.310, p=0.03). Both parameters were proved capable of discriminating AD converters from those MCI patients who remained stable, with sensitivity and specificity >75%. Our results suggest that conversion from MCI to AD is associated with a marked elevated N200 latency at baseline and a high increase in cytochrome c levels during a relatively short period of time, and that both parameters could be possibly considered as candidate markers for the discrimination between MCI patients who convert to AD and those who remain stable.

The proteins and the mechanisms of apoptosis: a mini-review of the fundamentals.

Apoptosis or programmed cell death is a physiological mechanism, characterized by specific morphological and biochemical changes such as cell shrinkage, chromatin condensation, protein cleavage, DNA breakdown and phagocytosis. Apoptosis is a significant contributor to the morphologic and functional development of multicellular organisms. It is also involved in the pathogenesis of several diseases including degenerative diseases of the central nervous system (CNS) like Alzheimer's disease or Parkinson's disease, cancer and immune system dysfunction. There are many factors, mainly proteins, which are involved in the activation, regulation and execution of related events. A fairly detailed outline of apoptotic mechanisms has also started to emerge and to be verified. In this short, focused mini-review, we attempt to outline current evidence regarding the mechanisms and the regulation of apoptosis.

Interleukin -1beta (IL-1 beta), interleukin 6 (IL-6) and tumor necrosis factor (TNF) in plasma and pleural fluid of pneumonia, lung cancer and tuberculous pleuritis.

Interleukins IL-1beta, IL-6 and TNF are increased in plasma of patients with severe infections and septic shock. Our objective was the evaluation of IL-1beta, IL-6 and TNF in plasma and exudates of pleural fluid and their contribution to the diagnosis. We studied 44 patients, 27 men and 17 women with mean age 66.81 +/- 11.75 years; 16 with pneumonia and parapneumonic effusion, 14 with primary lung cancer and pleural effusion and 14 with tuberculous pleuritis. We measured IL-1beta, IL-6 and TNF in serum and pleural fluid with ELISA. In patients with pneumonia and parapneumonic effusion the mean value of IL-1beta IL-6 and TNF in plasma was 9.05, 19.24 and 21.34 pg/ml and in pleural fluid 10.34, 32.19 and 25.30 pg/ml. In patients with lung cancer the mean values of IL-1beta, IL-6 and TNF were 5.33, 11.74 and 11.51 pg/ml and 6.70, 13.13, 20.89 pg/ml, respectively. In those with tuberculous pleuritis the respective mean values were 10.33, 49.94, 21.27 pg/ml and 14, 56.59, 23.58 pg/ml. In conclusion, IL-1beta and IL-6 were found increased in plasma and tuberculous pleural fluid, indicating an inflammatory status.

Utilising multimedia for training merchant mariners as paramedics.

MERMAID is a telemedicine project with global reach and a 24-hour, multilingual capability. It aspires to provide a model for the provision of health care services based on the electronic transmission of medical information, via ISDN based videoconferencing. This model is not limited to medical diagnostics but it encompasses all cases where the actual delivery of health care services involves a patient who is not located where the provider is. Its implementation requires the commissioning of an expensive telecommunications infrastructure and the exploration of a number of solutions. In fact, all categories of telemedical applications are considered while the full range of network choices is explored in terms of the cost/performance tradeoffs inherent to them and the developmental stage each of these options occupies in its life cycle. MERMAID utilises advanced land based line transmission technologies to aid the remote patient by making available the specialty care best suited to each particular case. Finally, the development of programme modules for training and education of the seafarers in the use of the MERMAID medical communications system is given top priority as such modules constitute the firmest basis for the promotion of proper practice of telemedicine at sea.

Intranet health clinic: Web-based medical support services employing XML.

In this paper, the implementation of an Internet-based telematic service for medical support is presented, which operates in pilot form within the INTRANET HEALTH CLINIC project--a two-year project supported by the European Commission under the Health Telematics Programme. The aim of the application is to offer high quality care to users of health services over inexpensive communication pathways, using Internet-based, interactive communication tools, like remote access to medical records and transmission of multimedia information. The XML technology was employed to achieve customised views on patient data, according to the access rights of different users. Strict security and access control policy were implemented to ensure secure transmission of medical data through the Internet. The system is designed to collaborate with existing clinical patient record systems and to be adjustable to different medical applications. Current pilot implementations are under clinical evaluation and include oncological patients (Greece), Lupus Erythrematosis (Canada), Obstetrics (Belgium) and Chronic Obstructive Pulmonary disease (Spain).

Medical emergency aid through telematics: design, implementation guidelines and analysis of user requirements for the MERMAID project.

MERMAID is an EU financed telemedicine project with global reach and 24-h, multilingual capability. It aspires to provide a model for the provision of health care services based on the electronic transmission of medical information, via ISDN based videoconferencing. This model will not be limited to medical diagnostics but it will encompass all cases where the actual delivery of health care services involves a patient who is not located where the provider is. Its implementation requires the commissioning of an expensive telecommunications infrastructure and the exploration of a number of solutions. In fact, all categories of telemedical applications (audio and video conferencing, multimedia communications, flat file and image transfer with low, medium and high bandwidth data requirements) are considered while the full range of network choices (digital land lines, cellular/wireless, satellite and broadband) are being tested in terms of cost/performance tradeoffs that are inherent to them and the developmental stage each of these options occupies in their in its life cycle. Finally, out that MERMAID utilises advanced land based line transmission technologies to aid the remote patient by making available the specialist care that is best suited in the particular case.

Induction of monocyte chemotactic protein-1 (MCP-1) and TNF alpha by Trichinella spiralis in serum of mice in vivo.

MCP-1 is a small (8-10 KDa) protein and a prototype member of the CC chemokine beta subfamily, which plays a critical role in acute and chronic inflammation. Recent evidence suggests an important role for MCP- 1, MCP-2 and MCP-3 in a number of pathological states, including delayed type hypersensitivity conditions, parasitic infections and rheumatoid arthritis. Forty BALB-c mice were treated with the parasite Trichinella spiralis. After the infection the animals were sacrificed at different periods from the initial infection and MCP-1 and TNFalpha were quantified in the mouse serum. The level of MCP-1 in the serum of mice infected with 100 larvae increases from 27.5+/-7.0 pg/ml at day 23, to a maximum level of 31.5+/-5.0 pg/ml at day 33, then decreased to 14.6+/-2.0 pg/ml at day 47. When the mice were infected with 200 larvae of T. spiralis the maximum increase was 34.4+/-2.5 pg/ml found on day 23. From day 33 to day 47 MCP-1 levels were decreased. In addition, in infected mice levels of TNFalpha were detectable in the serum as early as day 1. The level of TNFalpha was maximum at day 35 (3812+/-224 pg/ml). Serum from non-infected mice contained no detectable levels of either MCP-1 or TNFalpha. However, even if MCP-1 seems to be implicated in Trichinellosis, its exact role and function in inflammatory parasitic diseases remains to be determined.

A convincing case for the provision of telemedicine services to ocean going vessels: the MERMAID paradigm.

MERMAID is an EU financed telemedicine project with global reach and 24-hour, multilingual capability. It aspires to provide a model for the provision of health care services based on the electronic transmission of medical information, via ISDN based videoconferencing. This model will not be limited to medical diagnostics but it will encompass all cases where the actual delivery of health care services involves a patient who is not located where the provider is. Its implementation requires the commissioning of an expensive telecommunications infrastructure and the exploration of a number of solutions. In fact, all categories of telemedical applications (audio and video conferencing, multimedia communications, flat file and image transfer with low, medium and high bandwidth data requirements) are considered while the full range of network choices (Digital land lines, Cellular/Wireless, Satellite and Broadband) are being tested in terms of cost/performance tradeoffs that are inherent to them and the developmental state each of these options occupies in their in its life cycle. Finally, out that MERMAID utilises advanced land based line transmission technologies to aid the remote patient by making available the specialist care that is best suited in the particular case.

Relief for maritime medical emergencies through telematics.

MERMAID is a European Union (EU)-financed maritime telemedicine project with global reach and 24-h multilingual capability, so as to serve multinational crews working in the isolation of the world's oceans. It provides a model for the provision of healthcare services based on the electronic transmission of medical information via ISDN-based video conferencing. This model is not limited to medical diagnostics, but it encompasses all cases in which the actual delivery of healthcare services involves a patient who is not located where the provider is. Its implementation requires the commissioning of an extensive telecommunications infrastructure that includes both satellite transmission for ship to shore communication and an extensive ground-based network for summoning expert medical help from around the world so as to meet the project's multilinguality requirements and, therefore, the exploration of a number of solutions. In fact, all categories of telemedical applications (audio and video conferencing, multimedia communications, flat file and image transfer with low-, medium-, and high-bandwidth data requirements) are considered, while the full range of network choices (digital land lines, cellular/wireless, satellite, and broadband) are being tested in terms of cost/performance tradeoffs that are inherent to them and the developmental stage each of these options occupies in their lifecycle. Finally, out of that, MERMAID utilizes advanced land-based line transmission technologies to aid the remote patient by making available the specialist care that is best suited in the particular case.

ATTRACT--applications in telemedicine taking rapid advantage of cable television network evolution.

ATTRACT is a project that intends to provide telemedicine services over Cable Television Networks. ATTRACT is an European Commission funded project (Healthcare Telematics). The main objective of ATTRACT is to take advantage of emerging European Cable Television network infrastructures and offer cost-effective care to patients at home. This will be achieved through a set of broadband network applications that competitively provide low cost interactive health-care services at home. The applications will be based on existing or developing European Cable Television network infrastructures in order to provide all kind of users with affordable homecare services. It is ATTRACT's intention that citizens and users benefit from high quality access to home telemedical services which also implies cost savings for patients, their families and the already over burdened health institutions. In addition, the European industries will have extensive opportunities to develop, evaluate and validate broadband network infrastructures providing multimedia and interactive telemedical services at home. ATTRACT contributes to the EU telecommunications and telematics policy objectives that promote the development and validation of "applications and services" which "provide an intelligent telematic environment for the patient in institutions and other points of care that helps the patient to continue, as far as possible, normal activities and external communication".

Massive infiltration of basophilic cells in inflamed tissue after injection of RANTES.

Regulated upon activation normal T expressed and secreted (RANTES) is a new inducible protein member of the human C-C branch of chemokines. RANTES is a potent monocyte and lymphocyte chemoattractant and is a mediator of inflammatory responses. In these studies we found that RANTES 10 ng/50 microl chemoattracts basophilic cells in a dose-dependent manner 4 h after an intradermal injection in rat skin sites, as revealed by optic microscopy. Moreover, in biopsy specimens from rat skin injection sites histamine release was significantly higher (P < 0.05) than in controls (PBS 50 microl) after 4 h from RANTES treatment. The presence of basophilic cells in rat skin injection sites after RANTES-treatment was also confirmed by electron microscopy studies. In addition, histidine decarboxylase (HDC) mRNA was increased in rat skin sites injected with RANTES compared to sites injected with PBS (controls). Our report describes additional biological activities for RANTES, suggesting that this human chemoattractant protein may play a fundamental role in histamine and HDC generation, along with basophilic cell recruitment.