Telomere Length as a Marker of Biological Aging: A Critical Review of Recent Literature.

INTRODUCTION: Aging is characterized as a syndrome of deleterious, progressive, universal, and irreversible function changes affecting every structural and functional aspect of the organism and accompanied by a generalized increase in mortality. Although a substantial number of candidates for biomarkers of aging have been proposed, none has been validated or universally accepted. Human telomeres constitute hexameric repetitive DNA sequence nucleoprotein complexes that cap chromosome ends, regulating gene expression and modulating stress-related pathways. Telomere length (TL) shortening is observed both in cellular senescence and advanced age, leading to the investigation of TL as a biomarker for aging and a risk factor indicator for the development and progression of the most common age-related diseases. OBJECTIVE: The present review underlines the connection between TL and the pathophysiology of the diseases associated with telomere attrition. METHODS: We performed a structured search of the PubMed database for peer-reviewed research of the literature regarding leukocyte TL and cardiovascular diseases (CVD), more specifically stroke and heart disease, and focused on the relevant articles published during the last 5 years. We also applied Hill's criteria of causation to strengthen this association. RESULTS: We analyzed the recent literature regarding TL length, stroke, and CVD. Although approximately one-third of the available studies support the connection, the results of different studies seem to be rather conflicting as a result of different study designs, divergent methods of TL determination, small study samples, and patient population heterogeneity. After applying Hill's criteria, we can observe that the literature conforms to them weakly, with chronology being the only Hill criterion of causality that probably cannot be contested. CONCLUSION: The present review attempted to examine the purported relation between leukocyte TL and age-related diseases such as CVD and more specific stroke and heart disease in view of the best established, comprehensive, medical and epidemiological criteria that have characterized the focused recent relevant research. Although several recommendations have been made that may contribute significantly to the field, a call for novel technical approaches and studies is mandatory to further elucidate the possible association.

Age-related changes in electrogustometry thresholds, tongue tip vascularization, density, and form of the fungiform papillae in humans.

The aim of the study was to investigate age-related changes in electrogustometry (EGM) thresholds, in morphology and density of the fungiform papillae (fPap) and in vessels' shape and density at the tip of the human tongue.In 156 nonsmokers (74 males, 82 females; age range: 10-80 years), divided in age groups, EGM thresholds at the chorda tympani area, at the soft palate area, and at the area of the vallate papillae were recorded bilaterally. Morphology and density of the fPap and blood vessels' density and morphology at the tip of the tongue were examined using contact endoscopy (CE). EGM thresholds at the chorda tympani area were significantly higher in both men and women ←60 years of age than in younger individuals. At the soft-palatine area, EGM thresholds were significantly higher in men aged 20-29 years and ←60 years compared with men of other age groups. In women older than 50 years, thresholds at all 3 areas were significantly higher than in the younger age groups. No significant differences in EGM thresholds between the two sexes at all locations tested were detected. The density of fPap decreased significantly in men aged >50 years and in women aged >60 years compared with younger individuals. Vascular density decreased significantly and vascular morphology worsened at the tip of the tongue in subjects older than 60 years of age compared with younger subjects. The study showed statistically significant differences in EGM thresholds between the right and the left side of the tongue and between the two sexes. Aging is associated with a progressive increase in EGM thresholds. Density of fPap plays an important role for taste acuity in females aged >60 years and males aged ←50 years. Morphology of fPap and vessels' density and morphology at the tip of the tongue, as tested by CE, emerge as factors influencing taste function in subjects of both sexes aged >60 years.

Parathormone and 1,25(OH)2D3 but not 25(OH)D3 serum levels, in an inverse correlation, reveal an association with advanced stages of colorectal cancer.

Experimental, epidemiologic, and clinical trial data indicate the antineoplastic effects of calcium and vitamin D in large-bowel neoplasia. The aim of this study was to determine serum levels of vitamin D metabolites and parathormone (PTH) in patients with colorectal cancer (CRC) and to extract conclusions comparing their different levels in serum with healthy individuals. Group 1 (cancer patients) was consisted of 140 patients with CRC with clinical stages Duke's A: 12, B: 52, C: 62, and D: 14. Serum levels of 25(OH)D(3), 1,25(OH)(2)D(3), and PTH were determined in all patients. The findings are: (a) No significant difference was found in the serum levels of 25(OH)D(3) in each Duke's clinical stage in cancer patients, (b) serum 1,25(OH)(2)D(3) levels decreased with advanced cancer stages, and (c) serum levels of PTH showed a corresponding increase. Low serum levels of 1,25(OH)(2)D(3) on one hand and increased levels of PTH in patients with CRC on the other might be strongly related to the carcinogenetic process.

The clockwise rotation of myocardial fiber orientation from epicardial to endocardial surface in left ventricular free wall in a post-mortem human heart.

Following fixation and MRI imaging a post-mortem human heart was sliced at the sagittal plane. Each anatomical section was then cut into smaller segments and each one was objected to classical histology process. The resulting microscopy slides were digitalized with a scanner. The histological section reconstruction was achieved using Adobe Photoshop CS2(R). Using specific software, called FiberCad, the user can define and draw (with the assistance of optical microscope) those fibers that are parallel and those fibers that are vertical to the slides plane. To better align the histological 3D reconstruction, the software is equipped with an option that allows the user to make best possible fit between histological and MRI slices. We present the consequent sagittal sections of LV free wall (from epicardial to endocardial surface), whereby the clockwise rotation of the mean orientation of the fibers that are on the plane of sectioning is clearly evident. We present a post mortem analysis of the complete LV free wall of a human heart.

One heart, two bodies: a simulation study of body surface potential differences between donor and recipient of heart transplantation.

In cardiac transplantation has been recognized some "abnormalities" in recipient ECG. We investigated the influence of heart geometrical position within the chest cavity as well as somatometric parameters on body surface torso potentials. Two control patients with different Body Mass Index (BMI) were undergone a chest MRI scan. Using specific software we created two tetrahedral meshes that could be applied in our study. A post-mortem human heart was undergone a MRI scan and we also created its tetrahedral mesh. Using second software we extracted the heart mesh of control's torsos and we replaced them with the mesh of the post-mortem heart. The last program also assessed the influence of heart (re)positioning within the thorax, on the body surface potentials. The Finite Elements Method (FEM) was used to solve the forward electrocardiographic problem for both torsos, under the assumption that all the ventricular myocardium of the one post-mortem heart was excited. FEM was also applied in simulating Body Surface Potential Mapping (BSPM) on the first thorax torso for nine different heart positions. For BSPM, FEM has been applied on Poison equation. The results show higher BSPM in patient with lower BMI and significant changes in BSPM when heart was rotated round its long axis. Conversely, the heart shifts (long x- or y- axis) didn't cause significant changes on simulated BSPM.

Arrhythmogenesis in patients with stable chronic obstructive pulmonary disease.

OBJECTIVE: Fatal arrhythmias are a common cause of death in chronic obstructive pulmonary disease (COPD). Two major hypotheses for arrhythmogenesis in COPD have been proposed: arrhythmias are a consequence of hypoxaemia, hypercapnia or (tissue localised) acid-base disturbances, or arrhythmias are the result of the autonomic neuropathy that characterises COPD. Our objective was to verify these two hypotheses. METHODS: A total of 29 consecutive COPD patients (seven men and 22 women, mean age 63.75 +/- 10.50 years) were included in the study. Pulmonary function tests were performed and arterial blood gases were obtained simultaneously. Twelve-lead electrocardiograms were recorded from all patients. QT dispersion, which is a measure of myocardial repolarisation heterogeneity, and the coefficient of variation of the RR interval, which is a measure of heart rate variability, were calculated. RESULTS: Of the parameters measured, only the coefficient of variation of the RR interval appeared to be related to arrhythmias, since it correlated positively with arterial oxygen pressure (r = 0.418, statistical significance set at P < 0.05). CONCLUSIONS: Our results rule out the electropathy hypothesis and underline the role of autonomic neuropathy as the most probable arrhythmogenic mechanism in hypoxaemic COPD patients. Our interpretation is based on the fact that hypoxaemia decreases heart rate variability and on the strong association between the reduction in heart rate variability and arrhythmogenesis.

Expression of Co-stimulatory molecules on langerhans cells in lesional epidermis of human atopic dermatitis.

Langerhans cells (LC) are immature dendritic cells (DC) present in the skin epithelium. To understand the molecular and cellular mechanisms governing the inflammatory reaction in atopic dermatitis (AD), the expression of the LC specific marker CD1a, a member of major histocompatibility (MHC)-like glycoproteins, and the co-stimulatory molecules CD80 and CD86, expressed on functionally mature dendritic cells, were counted in lesional biopsies and normal epidermis by an immunohistochemical method. CD1a specific staining was observed in both normal and AD lesion specimens. CD80 and CD86 positive cells with morphological characteristics of the LC were found in lesional AD epidermis, suggesting a high level of functional maturity of these cells and their involvement in chronic inflammatory disease.

Visual function and visual perception in cerebral palsied children.

PURPOSE: To investigate visual function and perception in cerebral palsied (CP) children. METHODS: A total of 105 congenitally CP children (aged 6-15 years), without severe mental retardation, were classified into three groups: those with spastic quadriplegia, spastic diplegia and spastic hemiplegia. Data collected included patient history, IQ, refraction, far and near visual acuity, position of the eyes and eye movements, visual fields, colour perception, stereoacuity, slit lamp and fundoscopic examinations, and evaluation of visual perception. The results were compared with a control group from the general paediatric population. RESULTS: The IQ of the CP children ranged between 70 and 100. A total of 59% of them had best corrected distance visual acuity <6/6, with 25.5% <6/9. Near visual acuity was also reduced (70.1% scored <6/6 and 38.4% scored <6/9). Incidence of refractive errors was higher than in the control group (hypermetropia in 43.8% of the eyes, myopia 16.19% and astigmatism 40.9%) as was the incidence of strabismus (26.7% esotropic and 27.6% exotropic). In visual field testing, 80.95% of CP children were normal. A total of 94.28% had normal colour perception and 89.52% were free of ocular pathology. Stereopsis was abnormal or absent in 85.71% of the cases. Visual perception was markedly reduced: in 57.14% of the cases it was less than or equal to that of 6-year-old children; in 26.66% equal to that of 6- to 7.5-year-old children, and in 16.2% of the cases greater than or equal to that of 7.5-year-old children. CONCLUSIONS: In the absence of severe mental retardation, CP children have deficient visual skills. It is suggested that the poor visual skills of CP children are a separate, identifiable factor compounding the adverse effects of mental retardation.

Interpretation of spirometry through signal analysis.

Chronic obstructive pulmonary disease is attaining alarming proportions that requires more objective and quantitative ways for the diagnosis and the evaluation / stratification of, both, the disease and the therapeutic outcomes. Within this context, the present study explores the possibility to increase the effectiveness of spirometry through signal analysis. Expiratory flow results from converging airflows at different levels of airway branching. Furthermore, along a branching network of air conduits, the characteristics of converging air currents determine those of the resulting air flow. Thus, for the human bronchial tree, the characteristics of air currents within the smaller branches are, ideally, conserved at the expiratory flow recorded at the mouth. This makes it theoretically possible to use signal analysis methodologies in order to identify the characteristics of airflow along the different levels of the respiratory tree. The present study reports on an attempt to identify alterations non-invasively in the frequency spectrum of the first derivative of the Forced Vital Capacity curve of patients presenting with different respiratory conditions. Such alterations can be attributed to the onset and operation of the airway closure phenomenon that limits airflow, during forced expiration. Fundamental to the design of the study was the notion that the forced expiratory output of the respiratory system is determined by the bronchial tree and the upper respiratory tract. These two entities shape the air flow that is expelled from the collective airspace of the bronchial tree subdivisions distal to the terminal bronchi. At the end we were able to identify simple measures that are derived from the power spectrum of the derivative of the spirometric curve that permit the definition of specific filters and allow for the accurate classification of, at least, the basic types of respiratory disease.

Visual function and execution of microsaccades related to reading skills, in cerebral palsied children.

This article investigates the ability of cerebral palsied (CP) children to execute microsaccades. One-hundred and five congenitally CP school aged children (6 to 15 years old), without severe mental retardation, were classified into three groups: those with spastic quadriplegi, spastic diplegics, and spastic hemiplegics on the basis of: (1) patient anamnesis, (2) IQ estimation, (3) evaluation of the microsaccadic skills with the Developmental Eye Movement test (DEM). Their performance in these tests was compared with a control group from the general pediatric population. IQ of the CP children ranged between 70 and 100; the microsaccadic skills were severely affected: only 19% of the CP children had normal function, 20.9% of the CP children appeared with a pure oculomotor problem, 32.4% of the CP children had a visual-perceptual problem, and 27.7% of the CP children had a combined oculomotor and visual perceptual problem. CP children, in the absence of severe mental retardation, have disturbed visual skills and visual perception that usually leads to reading difficulties. It is also suggested that microsaccadic skills of CP children is an identifiable factor compounding the adverse effects of mental retardation on reading skills.

A training network for introducing telemedicine, telecare and hospital informatics in the Adriatic-Danube-Black Sea region.

DIMNET is a training mechanism for a region of central Europe. The aim is to upgrade the information technology skills of local hospital personnel and preserve their employability following the introduction of medical informatics. DIMNET uses Internet-based virtual classrooms to provide a 200-hour training course in medical informatics. Training takes place in the cities of Drama, Kavala, Xanthi and Varna. So far, more than 600 people have benefited from the programme. Initial results are encouraging. DIMNET promotes a new vocational training culture in the Balkans and is supported by local governments that perceive health-care as a fulcrum for economic development.

The Varna-Thessaloniki telemedical collaboration in setting up a regional transborder transplantation network.

In most Balkan countries, with the exception of Greece, transplantation is very rare and equality of access does not exist. In 2003, a Balkan partnership was established called SETNET (South-Eastern European Transplantation Network) for the promotion of transplantation. The objectives are to bring about the diffusion of transplantation techniques and practices in the Balkans, to increase public support for and participation in transplantation, and to eliminate the disparities in access to good health-care. SETNET is already beginning to generate data for an analysis of transplantation-related needs in the Balkans and to accelerate cross-border data exchange in transplantation-related emergencies. In the next few years, a regional training programme will be introduced for all health-care staff involved in transplantation. A regional organ procurement and transplantation network will be set up to utilize the existing telemedicine infrastructure. If successful, it will also prove that telemedicine infrastructures, however modest, can be the backbone for other, far-reaching human networks.

A simple telemedicine system to provide second-opinion advice to the patients of an Albanian diagnostic centre.

Since August 2003, the IKEDA Klinika diagnostic centre in Tirana, Albania, has offered patients telemedical help from Greece. The teleconsultation service is based on Internet technologies adapted to telemedical use, including the use of forms (e.g. for the patient history), multimedia file exchanges (e.g. for radiographs and electroencephalograms) and videoconferencing. The teleconsultants assist in treatment planning and, when necessary, in organizing the transfer of patients to Greece. The four cornerstones of the service are: the provision of second opinions by telemedicine; assistance in treatment planning; assistance to patients during transfer; and the continuity of medical care on their repatriation. Based on the first six months of operation, we estimate that, if bureaucratic visa restrictions to patient movement between Albania and Greece are removed, more than 2000 patients per year will benefit from the service and more than 400 patients will be transferred to Greek hospitals for treatment.

Real time estimation of physical activity and physiological performance reserves of players during a game of soccer.

The need for ever increasing achievements in athletic performance is pushing the acquisition costs and salaries of top performers to unprecedented heights. Individual talent, good physical condition and relentless training, however, do not by themselves guarantee success of the team effort. Team performance is determined by game strategy and team coordination. Ideally, during a game, the team coach should be able to gauge the instantaneous physical condition and performance reserves of each player on the team and direct game strategy accordingly. Our experimental setup explores the feasibility of objectively estimating, in real time, the intensity of physical activity and the physiological performance reserves of each and every player on the team during a game of soccer.

The Korydallos, Greece, prisons telemedicine system experience: why technology alone is not a sufficient condition.

In 1999 the Greek Ministry of Justice decided to utilise telemedicine to improve health services in the largest prison in Greece (Korydallos Prison). The Nikea Hospital in Piraeus undertook to support the effort. For 12 months following installation, intensive "hands-on" training on the use of the system was offered to the staff of both the Korydallos Prison and the Nikea Hospital. However serious operational problems related either to prison bureaucracy or to the inflexibility the Greek National Health Service has annulled the effectiveness of the Korydallos Prison telemedicine system. Still, analysis of the system development history reveals that: (1) if freed from bureaucratic and labour related obstacles, prison telemedicine is a viable option. (2) Telemedicine can avert transfers to out-of-prison medical facilities. (3) If properly implemented, telemedicine can generate substantial savings and (4) telemedicine can greatly improve the quality of care available to prisoners.

A clinical and educational telemedicine link between Bulgaria and Greece.

During its transition to a free economy, Bulgaria benefited from foreign aid provided by Greece. One of the projects was the clinical and educational telemedicine link between the Medical University of Varna in Bulgaria and the Faculty of Medicine of Aristotle University of Thessaloniki in Greece. This began in 1997. In terms of the educational activities, the Bulgarian side of the network supports (a) electronic design and publishing activities, (b) web hosting and mail server activities and (c) satellite communications. In addition it supports an electronic classroom equipped with personal workstations, multimedia projectors and videoconference facilities. Communications are via the ISDN network. In terms of its telemedicine activities, the network provides remote medical assistance to "language handicapped" travellers and to migrant workers in both countries. The main clinical experience is remote consultations in immunology. This admittedly limited experience demonstrates that telemedicine can be used to provide assistance to remote colleagues. In cases where the patient cannot communicate with the attending physician, the use of telemedicine can greatly improve the quality of care available to travellers and migrant workers.

A clinical and educational telemedicine link between Bulgaria and Greece.

During its transition to a market economy, Bulgaria benefited from foreign aid provided by Greece. One of the projects was the clinical and educational telemedicine link between the Medical University of Varna in Bulgaria and the Faculty of Medicine of Aristotle University of Thessaloniki in Greece. This began in 1997. In terms of the educational activities, the Bulgarian side of the network supports: an electronic classroom equipped with personal workstations, multimedia projectors and videoconference facilities; electronic design and publishing activities; Web hosting and mail server activities; and satellite communications. Communications are via ISDN. The main clinical experience has been remote consultations in immunology. This experience (admittedly limited) demonstrates that telemedicine can be used to provide assistance to remote colleagues. In addition, the use of telemedicine can greatly improve the quality of care available to travellers and migrant workers in cases where the patient cannot communicate with the attending physician because of a language barrier.

Developing prison telemedicine systems: the Greek experience.

Prison telemedicine systems operate in circumstances in which the provision of medical care is very expensive. In 1999 the Greek Ministry of Justice decided to use telemedicine to improve health services in the largest prison in Greece (Korydallos Prison, in Athens). The Nikea Hospital in Piraeus undertook to support the effort in order: to enable prison paramedics and guards to call for remote evaluation of inmates when the prison's doctors were off duty; to provide second opinions; and to allow screening and primary care coverage for inmates through teleconsultations with Nikea Hospital specialists. For 12 months following installation, intensive 'hands-on' training on the use of the system was offered to the staff of both the Korydallos Prison and the Nikea Hospital. In all, 400 physicians, nurses and paramedics were trained. Despite all this effort, there were serious operational problems related either to prison bureaucracy or to the inflexibility of the Greek national health system, which annulled the effectiveness of the prison telemedicine system. The experience suggests that prison telemedicine is a viable option if freed from bureaucratic and labour-related obstacles, and can improve the quality of care available to prisoners.