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Biomedical subjects

Angel García

Publications and source records attributed to Angel García.

26 records · Page 2Linked to original sources

Management of patients with diabetes through information technology: tools for monitoring and control of the patients' metabolic behavior.

BACKGROUND: The junction of telemedicine home monitoring with multifaceted disease management programs seems nowadays a promising direction to combine the need for an intensive approach to deal with diabetes and the pressure to contain the costs of the interventions. Several projects in the European Union and the United States are implementing information technology-based services for diabetes management using a comprehensive approach. Within these systems, the role of tools for data analysis and automatic reminder generation seems crucial to deal with the information overload that may result from large home monitoring programs. The objective of this study was to describe the automatic reminder generation system and the summary indicators used in a clinical center within the telemedicine project M2DM, funded by the European Commission, and to show their usage during a 7-month on-field testing period. METHODS: M2DM is a multi-access service for management of patients with diabetes. The basic functionality of the technical service includes a Web-based electronic medical record and messaging system, a computer telephony integration service, a smart-modem located at home, and a set of specialized software modules for automated data analysis. The information flow is regulated by a software scheduler, called the Organizer, that, on the basis of the knowledge on the health care organization, is able to automatically send e-mails and alerts notifications as well as to commit activities to software agents, such as data analysis. Thanks to this system, it was possible to define an automatic reminder system, which relies on a data analysis tool and on a number of technologies for communication. Within the M2DM system, we have also defined and implemented a number of indexes able to summarize the patients' day-by-day metabolic control. In particular, we have defined the global risk index (GRI) of developing microangiopathic complications. RESULTS: The system for generating automatic alarms and reminders coupled with the indexes for evaluating the patients' metabolic control has been used for 7 months at the Fondazione Salvatore Maugeri (FSM) in Pavia, Italy. Twenty-two patients (43 +/- 16 years old, 12 men and 10 women) have been involved; six dropped out from the study. The average number of monthly automatic messages was 29.44 +/- 9.83, i.e., about 1.8 messages per patient per month. The number of monthly alarm reminders generated by the system was 16.44 +/- 4.39, so that the number of alarms per patient was about 1. The number of messages sent by patients and physicians during the project was about 13 per month. The GRI analysis shows, during the last trimester, a slight improvement of the performance of the FSM clinic, with a decrease in the percentage of badly controlled values from 33% to 27%. Finally, we found the presence of a linear increasing correlation between the mean GRI values and the number of alarms generated by the system. CONCLUSIONS: A telemedicine system may incorporate features that make it a suitable technological backbone for implementing a disease management program. The availability of data analysis tools, automated messaging system, and summary indicators of the effectiveness of the health care program may help in defining efficient clinical interventions.

Diabetes Mellitus↗

Immunohistochemical staining for p16 and p53 in premalignant and malignant epithelial lesions of the vulva.

Two distinct types of vulvar squamous cell carcinomas and their precursors, vulvar intraepithelial neoplasias (VIN), which differ in terms of clinical presentation and behavior, have been delineated. Human papillomavirus (HPV)-associated carcinomas are of basaloid or warty type, whereas tumors unrelated to HPV are usually keratinizing and differentiated. Thus, the major stratifying factor for vulvar carcinomas and VIN is their etiopathogenetic relationship with HPV. However, because of technical difficulties in confidently detecting HPV in tissues, this diagnosis is usually based on purely morphologic criteria, even though some overlap exists between these histologic types. Recently, the tumor suppressor protein p16 has been shown to be specifically overexpressed in HPV-related carcinomas and premalignant lesions of the uterine cervix, oral cavity, and anus, but the presence of p16 vulvar squamous lesions has not been examined. We have evaluated the immunohistochemical expression of p16 in a series of formalin-fixed, paraffin-embedded vulvar carcinomas and their putative precursors. p16 was strongly positive in all cases of basaloid/condylomatous VIN3 (30/30) and basaloid (7/7) and warty (3/3) carcinomas. In contrast, p16 was almost consistently negative in normal skin, squamous cell hyperplasia (0/20), lichen sclerosus (0/19), differentiated (simplex) VIN3 (0/11), verrucous carcinoma (0/2), and keratinizing squamous cell carcinoma (3/33, 9%). One of the keratinizing squamous cell carcinomas positive for p16 occurred in a 25-year-old woman and the other two were associated with small foci of basaloid VIN3 adjacent to the tumor, suggesting a probable relationship with HPV. p16 was positive in 6 of 10 of basal cell carcinomas. In conclusion, p16 immunostaining is a good discriminator between HPV-associated and HPV-unrelated vulvar carcinomas and VIN, although it cannot differentiate basaloid squamous and basal cell carcinoma.

Adolescent↗

Differential proteome analysis of TRAP-activated platelets: involvement of DOK-2 and phosphorylation of RGS proteins.

We have applied a proteomics approach to analyze signaling cascades in human platelets stimulated by thrombin receptor activating peptide (TRAP). By analyzing basal and TRAP-activated platelets using 2-dimensional gel electrophoresis (2-DE), we detected 62 differentially regulated protein features. From these, 41 could be identified by liquid chromatography-coupled tandem mass spectrometry (LC-MS/MS) and were found to derive from 31 different genes, 8 of which had not previously been reported in platelets, including the adapter downstream of tyrosine kinase 2 (Dok-2). Further studies revealed that the change in mobility of Dok-2 was brought about by tyrosine phosphorylation. Dok-2 tyrosine phosphorylation was also found to be involved in collagen receptor, glycoprotein VI (GPVI), signaling as well as in outside-in signaling through the major platelet integrin, alpha IIIb beta 3. These studies also provided the first demonstration of posttranslational modification of 2 regulator of G protein signaling (RGS) proteins, RGS10 and 18. Phosphorylation of RGS18 was mapped to Ser49 by MS/MS analysis. This study provides a new approach for the identification of novel signaling molecules in activated platelets, providing new insights into the mechanisms of platelet activation and building the basis for the development of therapeutic agents for thrombotic diseases.

Adaptor Proteins, Signal Transducing↗

[Dilated cardiomyopathy and autoimmunity: an overview of current knowledge and perspectives].

The diagnosis of idiopathic dilated cardiomyopathy is assigned to patients with left ventricular systolic dysfunction and dilatation in the absence of any other documented cause. Idiopathic dilated cardiomyopathy is presumed to have a multifactorial origin, possibly including autoimmune mechanisms. We reviewed the current state of knowledge of this topic, including a pathophysiological hypothesis postulating a relation between an autoimmune process and sympathetic over-stimulation and systolic dysfunction. The implications for therapy are considered in the light of experience with other autoimmune diseases. The results of immunosuppressant treatment and preliminary experiences with immunoadsorption are reviewed and their future perspectives are discussed.

Adjuvants, Immunologic↗

MEM and Nott dynamic retinoscopy in patients with disorders of vergence and accommodation.

The accommodative response in 34 patients with accommodative and binocular disorders was assessed with two different techniques of dynamic retinoscopy used in clinical practice: monocular estimate method (MEM) and Nott retinoscopy. The data obtained by both techniques were compared, evaluating the correlation and agreement between them. Results showed that there were statistically significant differences between the techniques with MEM values being more plus than Nott ones. There was a high correlation between the two techniques (0.90) and the regression analysis indicated that a linear relationship existed between MEM and Nott dynamic retinoscopy, so that accommodative lag value for Nott dynamic retinoscopy would be calculated by dividing the MEM result by 2. However, although both retinoscopies were related, there was a lack of agreement between them (+/-0.53 D) indicating that the two methods are not interchangeable for clinical purposes.

Accommodation, Ocular↗

Diagnostic signs of accommodative insufficiency.

PURPOSE: To determine which are the most sensitive tests, together with accommodative amplitude, to classify accommodative insufficiency (Al), we analyzed the relation between monocular estimated method (MEM) dynamic retinoscopy, monocular and binocular accommodative facility (MAF, BAF), and positive relative accommodation (PRA) with or without the presence of reduced amplitude of accommodation. METHODS: We studied 328 symptomatic patients who presented consecutively to an optometric clinic. From this sample, we selected the 41 patients who presented amplitude of accommodation at least 2 D below the minimum age-appropriate amplitude according to Hofstetter's formula: 15 - 0.25 x age. We also selected data from 40 consecutive subjects (control group) with no general binocular disorders and normal accommodative amplitudes. We studied the specificity and sensitivity of the four signs related with the accommodative insufficiency: high MEM dynamic retinoscopy, failing MAF and BAF with minus lenses of +/- 2 D flipper lenses, and low PRA. RESULTS: Using the standard deviation as the cutoff, the specificity values were MEM = 0.88, MAF = 1, BAF = 0.93, and PRA = 1. When using the mean value as the cutoff, the specificity diminished, fundamentally for MEM. The sensitivity for the 41 patients using standard deviation as the cutoff was MEM = 0.44, MAF = 0.34, BAF = 0.27, and PRA = 0.27, and when using the mean value as the cutoff the four, sensitivity values increased. CONCLUSIONS: According to the sensitivity results, with both cutoffs used, failing the +/- 2 D MAF test seems to be the sign that is most associated with the accommodative insufficiency.

Accommodation, Ocular↗

Evaluating relative accommodations in general binocular dysfunctions.

PURPOSE: To examine the relationship between relative accommodation and general binocular disorders and to establish their importance in the diagnosis of these anomalies. METHODS: We analyzed data of negative relative accommodation (NRA) and positive relative accommodation (PRA) in 69 patients with nonstrabismic binocular anomalies. RESULTS: Statistical analysis showed that low values of NRA and PRA were not associated with any particular disorder. High values of PRA (> or = 3.50 D) were related to the disorders associated with accommodative excess, whereas high values of NRA (> or = 2.50 D) were not related to accommodative excess. Statistical differences suggested that a high value of PRA could distinguish between anomalies. Sensitivity analysis revealed that high PRA was the most sensitive sign in patients with convergence insufficiency combined with accommodative excess (0.89) and one of the most sensitive signs for subjects with accommodative excess (0.72) and for those with convergence excess combined with accommodative excess (0.70). CONCLUSIONS: Anomalous results of NRA were not clearly associated with any dysfunction. High values of PRA were related to disorders associated with accommodative excess, so the sign of a high value of PRA should be considered as one of the diagnostic signs of these anomalies.

Accommodation, Ocular↗

Applying proteomics technology to platelet research.

Platelets are small enucleated cells that circulate in the blood, where they play a key role in hemostasis and contribute to the formation of vascular plugs. Pathologically, they are involved in thrombosis and heart disease. Because platelets do not have a nucleus, proteomics offers a powerful way to approach their biology. Proteomics technology is based on the huge analytical power offered by mass spectrometry in combination with several separation techniques, such as two-dimensional gel electrophoresis (2DGE) or multidimensional liquid chromatography. Proteomics provides information about the complete set of proteins present in platelets, the platelet proteome, including post-translational variants. Over the last years, several research groups have applied proteomics to platelet research. A detailed analysis of the general proteome and signaling cascades in human platelets will improve our knowledge of platelet function, and thereby aid the development of new therapeutic agents to treat thrombotic diseases. This review presents the major advances in mass spectrometry-based proteomics techniques and their application to platelet research, and analyzes in detail the most relevant contributions to the field.

Biotechnology↗