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Biomedical subjects

S Forti

Publications and source records attributed to S Forti.

At least 19 recordsLinked to original sources
PubMed2003

Monoclonal antibody to fibulin-1 generated by genetic immunization.

Fibulin-1 (Fbln-1) is an extracellular matrix (ECM) and plasma glycoprotein. Considering the growing evidence indicating that Fbln-1 plays a role in cancer we sought to develop monospecific antibodies to better facilitate further studies of the function of Fbln-1 in breast cancer. Using a plasmid expression vector encoding full-length human Fbln-1D as an immunogen and CpG oligodeoxyribonucleotides as adjuvant a monoclonal antibody (MAb) against Fbln-1 was produced. This MAb, designated MEM-2 was of IgM isotype and reacted with bacterially expressed Fbln-1. Furthermore, MEM-2 reacted with Fbln-1 expressed in the ECM released by cultured human breast carcinoma SKBR-3 cells in ELISA, and also with Fbln-1 present in SKBR-3 cell extract in immunoprecipitation and Western blotting. MEM-2 also reacted with Fbln-1 in human breast carcinoma specimens. These findings illustrate the utility of genetic immunization as a means of generating monoclonal antibodies to tumor-related ECM proteins. MEM-2 represents a useful new tool for the study of Fbln-1 in breast cancer.

Adjuvants, Immunologic↗
PubMed2003

Analysis of user-satisfaction with the use of a teleconsultation system in oncology.

There is an increasing interest in assessing telemedicine as alternative method of delivering high quality cancer treatment to patients living in rural areas. In the Province of Trento (north-east Italy) a tele-oncology system was implemented to provide non-surgical oncological consultation to district general hospitals. The aim of this study was to explore user-satisfaction with the system after 6 months of experimentation. During the on-field validation two questionnaires with open and closed-response questions were distributed to 80 physicians and nurses 6 months apart to investigate the users' expected benefits vs. perceived ones. The two questionnaires were compared to assess how perceived benefits differed from expected ones. Significant differences were found regarding improvements in: the standardization of diagnostic-therapeutic procedures using the Electronic Patient Record (EPR)]; information sharing; data updating; consultation speed; and the possibility to diminish patients' travels through the use of teleconsultation (TC). Physicians' responses showed a significant difference regarding the EPR's effects on relationship with patient, the nurses' responses with regards to its effects on care quality. Physicians felt that both modalities of teleconsultation were useful in enhancing communication with colleagues (86% for the synchronous TC, 80% for the asynchronous TC). Responses indicated that the major difficulties encountered were in the introduction of the system into the daily routine. Despite this, user expectations for its future use in clinical field were considerably high.

Attitude of Health Personnel↗
PubMed2002

An evaluation of the use of and user satisfaction with a teleconsultation system in oncology practice.

A three-year oncology teleconsulting project was concluded in November 2000. During a six-month study period, 38 clinical physicians and 47 nurses used the system. A total of 617 electronic patient records were created in the oncology department, 297 in dermatology and 24 in gynaecology. There were 45 synchronous teleconsultations involving various participants, lasting a total of 708 min. We conducted surveys of the attitudes of users to the teleconsulting system both before and after its implementation. There were no significant differences between the two surveys and the results showed that users had a positive reaction to the system and high expectations of its future utilization.

Attitude of Health Personnel↗
PubMed2001

The virtual case: a new method to completely digitize cytological and histological slides.

The purpose of this study was to present a new method for handling histological/cytological cases. Thanks to the introduction of information technology in pathology, including the amenities afforded by robotic microscopes and digital imaging, tissue slides can be represented and evaluated using digital techniques in order to construct virtual cases through completely automated procedures. A virtual case (VC) is composed of a collection of digital images representing a histological/cytological slide at all magnification levels together with all relevant clinical data. In the present study, we describe an automated system to manage robotic microscope and image acquisition for the proper construction of VCs. These can then be viewed on a computer by means of an interface ("user-friendly") that allows one to select the more appropriate fields and to examine them at different magnifications, rapidly going from panoramic views to high resolution and vice versa. In comparison with glass slides, VCs have several advantages arising from their digital nature and can be considered a common platform for a wide range of applications such as teleconsultation, education, research, and quality control and proficiency tests.

Analog-Digital Conversion↗
PubMed2001

Prevention of spontaneous neu-expressing mammary tumor development in mice transgenic for rat proto-neu by DNA vaccination.

The HER-2/neu proto-oncogene is overexpressed in 20-30% of human breast cancers and is associated with high recurrence risk. The oncogenic potential of HER-2/neu, together with its elevated expression in tumors, cell surface localization, and immunogenicity in some patients, make this oncoprotein an ideal target for immunotherapeutic approaches. To test the efficacy of immune-based strategies in eliciting an antitumor response, we used the N#202 transgenic mouse model engineered to overexpress the rat neu proto-oncogene under the control of the mouse mammary tumor virus promoter; females of this line develop spontaneous focal mammary tumors by 6 months of age. Transgenic mice immunized intramuscularly with a HER-2 cDNA ligated into the VR1012 (VICAL) expression vector under the control of the cytomegalovirus promoter developed significantly fewer spontaneous tumors as compared with mice injected with the empty vector (P < 0.0001) or not injected (P = 0.0006). However, this protection was observed only when immunization was started in 3-month-old but not in 6-month-old mice. These data suggest that the xenogeneic HER-2 DNA sequence can break immune tolerance to rat neu in transgenic N#202 mice and induce protective immunity that impairs the neu oncogene-driven progression of mammary carcinogenesis. The preventive effect achieved by our immunological approach appeared not to be based on anti-neu specific B and T cell immune attacks but was more possibly based on different mechanisms including aspecific and inflammatory immunological responses.

Age Factors↗
PubMed2001

Robotic telepathology for intraoperative remote diagnosis using a still-imaging-based system.

The aim of the present study was to assess whether a telemicroscopy system based on static imaging could provide a remote intraoperative frozen section service. Three pathologists evaluated 70 consecutive frozen section cases (for a total of 210 diagnoses) using a static telemicroscopy system (STeMiSy) and light microscopy (LM). STeMiSy uses a robotic microscope, enabling full remote control by consultant pathologists in a near real-time manner. Clinically important concordance between STeMiSy and LM was 98.6% (95.2% overall concordance), indicating very good agreement. The rates of deferred diagnoses given by STeMiSy and LM were comparable (11.0% and 9.5%, respectively). Compared with the consensus diagnosis, the diagnostic accuracy of STeMiSy and LM was 95.2% and 96.2%. The mean viewing time per slide was 3.6 minutes, and the overall time to make a diagnosis by STeMiSy was 6.2 minutes, conforming to intraoperative practice requirements. Our study demonstrates that a static imaging active telepathology system is comparable to dynamic telepathology systems and can provide a routine frozen section service.

Diagnostic Imaging↗
PubMed2001

[Telemetric intraoperative diagnosis among hospitals in Trentino: first evaluations and optimization of the procedure].

Telemetric, intraoperative frozen section diagnosis may be a useful tool for rural hospitals lacking an in-house pathology service. As a part of a Health Ministry Project on Telemedicine in Trentino (northern Italy), we developed a static telemicroscopy system (STeMiSy). This system connects the rural hospital of Cles with the main hospital of Trento. The two hospitals are 40 kilometers apart, and the road connecting the two towns runs across the mountains and has a heavy traffic. Before putting STeMiSy into practice, we tested the software and hardware on the LAN of the regional hospital system, by connecting the pathology services of Trento and Rovereto (20 kilometers apart). This test phase lasted three months and has not revealed major problems in the LAN nor in the robotic microscope, which was always precise and reliable. The quality of the images and the speed of transmission were largely sufficient for intraoperative frozen section diagnosis. Minor details of the histological slides were not always appreciated on the panoramic view. This loss of some details may be due to the quality of the panoramic view, which represents the 'surfing map' to read the cases. Nevertheless, the recognition of these small details was not so relevant as to change the surgical approaches. An audioconference system, utilizing the same transmission channel, not only slightly slowed the transmission but also caused some instability to the system. The audioconference system has therefore been abandoned, and when necessary we used the normal telephone. Macroscopic images of the whole surgical specimen, the surgeon's responsibility for the sampling, good technical quality of the slide, and good training will allow us to perform remote frozen section diagnosis in the absence of the pathologist. We believe that the main, and probably only, difficulty for this approach is not of a technical nature, but reflects the pathologist's resistance to making a remote video diagnosis.

Attitude of Health Personnel↗
PubMed2000

Design and initial implementation of a regional tele-oncology project.

Two tele-oncology projects have been in progress since 1997 in the Province of Trento in north-east Italy. The common aim of the projects concerns the design and the implementation of a non-surgical tele-oncology system intended to provide a flexible computing environment for the joint management of oncology patients in a wide-area network. The two projects involve both hospital specialists and general practitioners treating oncological patients. The first phase of the project involves the design and implementation of the oncology teleconsultation service.

Humans↗
PubMed1997

Calcium-antagonist effects of norbormide on isolated perfused heart and cardiac myocytes of guinea-pig: a comparison with verapamil.

1. Cardiac effects on norbormide and verapamil were compared in single ventricular myocytes, right atria, and Langendorff perfused hearts isolated from guinea-pigs. 2. In ventricular myocytes, norbormide 50 microM inhibited the peak calcium current (ICa) by 49.6 +/- 3.9% without altering the shape of the current-voltage relationship; verapamil 1 microM inhibited ICa by 83.2 +/- 3.3%. Neither norbormide nor verapamil affected ICa at the first beat after a 3 min quiescence period; during repeated depolarizations, both drugs cumulatively blocked ICa (use-dependence), with time constants of 23.0 +/- 7.0 s for norbormide and 91.3 +/- 8.4 s for verapamil. 3. In constant-flow perfused hearts electrically driven at 2.5 Hz or 3.3 Hz, both norbormide and verapamil concentration-dependently decreased ventricular contractility (dP/dtmax), atrio-ventricular (AV) conduction velocity and coronary pressure. Intraventricular conduction velocity was slightly decreased by norbormide but not by verapamil. At an equivalent change in AV conduction, norbormide depressed heart contractility less than verapamil. The effects of norbormide on AV conduction, intraventricular conduction, and contractility were frequency-dependent. Furthermore, the curves correlating the mechanical and electrical effects of norbormide at the two frequencies used were apparently coincident, while those of verapamil were clearly separated. 4. In spontaneously beating right atria, norbormide and verapamil decreased the frequency of sinus node (SA) in a concentration-dependent way. At an equivalent effect on the AV conduction, norbormide exerted a greater effect on sinus frequency than verapamil. 5. These results indicate that in guinea-pig heart norbormide has the pharmacological profile of a Ca-antagonist with strong electrophysiological properties. In comparison with verapamil, norbormide is more selective on SA and AV node tissues and exerts a weaker negative inotropic effect on ventricles. In principle, this pattern of effects may be an advantage in treating supraventricular tachyarrhythmias in patients with heart failure. The effect of norbormide on intraventricular conduction may represent an additional antiarrhythmic mechanism.

Animals↗
PubMed1997

Expert pathology consultation through the Internet: melanoma versus benign melanocytic tumours.

Twenty consecutive cases of melanocytic lesions were chosen from the archives of the archives of the institute of Anatomic Pathology at Santa Chiara Hospital, Trento. Representative images were acquired at a spatial resolution of 512 x 512 pixels, saved in IPEG format and delivered to the remote pathologist by multimedia internet electronic mail. Six cases were diagnosed as benign melanocytic lesions by the local pathologist. Of the 20 cases transmitted, each with an average of 5.3 images, the remote pathologist suggested a diagnosis of malignancy in nine cases while 10 cases were thought to be benign. In one case the images were not considered sufficient for diagnosis. Overall, the diagnostic agreement between local and remote pathologist was 79% (kappa = 0.58, P = 0.002). This preliminary study suggest that telepathology by internet electronic mail can be a valuable tool for remote consultation in dematopathology, as well as for other diagnostic fields where expert consultation is necessary.

Computer Communication Networks↗
PubMed1997

Fine-needle aspiration cytology of the breast: a preliminary report on telepathology through Internet multimedia electronic mail.

Telepathology is a field of telemedicine that enables the exchange of histologic and cytologic images for consultations among pathologists of two or more remote institutions, through a suitable communication channel. The Internet can connect several scientific and medical institutions because of the existence of a set of standard protocols that allow different computers to communicate; multimedia electronic mail is one such protocol, which allows asynchronous transmission of multimedia documents, i.e., including text, images, movies, and sounds. The aim of the present article is to test a novel approach in which Internet multimedia electronic mail is used as a communication medium to obtain an asynchronous telepathology tool for remote consultation. To assess the diagnostic validity of the method, 48 cases of fine-needle aspiration cytology of breast lesions were sent from Udine to Trento, Italy. Comparisons between local and remote diagnoses, and cytologic diagnoses versus subsequent histologic reports demonstrated that Internet multimedia electronic mail is suitable for remote consultation. Internet multimedia electronic mail thus presents an additional diagnostic tool that is easy to use, available on a wide range of computers, and inexpensive, because its cost is independent of distance.

Biopsy, Needle↗
PubMed1996

Telepathology using Internet multimedia electronic mail: remote consultation on gastrointestinal pathology.

The feasibility of using the Internet for remote pathology consultation was examined. We assessed the diagnostic agreement between two groups of pathologists who independently evaluated histopathological cases exchanged by Internet electronic mail. The exchange was between two different workstations using readily available software not specifically developed for telemedicine. Data and images from 76 cases were transmitted to four pathologists. An average of 4.5 images per case were transmitted at compression ratios of between 6:1 and 40:1, corresponding to 250 kByte of data per case. In two cases the remote pathologists could not make a diagnosis. Agreement was reached in 63 of the other 74 (kappa = 0.79). In 11 cases (15%) there was a misdiagnosis. However, the results are encouraging and suggest that Internet electronic mail can be used successfully for remote consultation in pathology.

Computer Communication Networks↗
PubMed1996

Grading in superficial papillary bladder carcinoma, with an emphasis on nuclear orientation.

OBJECTIVE: To develop a computerized analysis method that could reflect not only cellular anaplasia but also the orientation (PV) of neoplastic elements and could allow the separation of low (grade G 1 and G 2a) and high (G 2b) grades of superficial papillary bladder tumors (SPBTs). STUDY DESIGN: Cellular anaplasia is based on classic morphometric parameters, such as mean and standard deviation of area, perimeter, roundness and aspect ratio (length/width ratio) of 50 papillary bladder tumors (16 G 1, 10 G 2a and 24 G 2b according to Pauwels). Orientation of the major axis of each nucleus with respect to the true basal membrane was calculated using the SD of valve distribution. RESULTS: No statistically significant differences were found between cases showing contiguous grades (G 1 versus G 2a or G 2a versus G 2b). PV, SD of the area and SD of the perimeter were the parameters that could significantly distinguish between G 1 and G 2b and between G 1 plus G 2a and G 2b (P < .05). When comparing G 1 with G 2a plus G 2b, only PV and SD of the area were statistically significant. CONCLUSION: Quantification of the irregularities in the orientation of nuclei with respect to the basal membrane may improve morphometric classification of low grade SPBTs.

Cell Nucleus↗
PubMed1995

Distinct patterns of calcium transients during early and delayed afterdepolarizations induced by isoproterenol in ventricular myocytes.

BACKGROUND: The relation between early afterdepolarizations (EADs) and changes in intracellular Ca2+ concentration ([Ca2+]i) is still unclear. In the present study, we compared spatiotemporal changes in [Ca2+]i related to EADs and delayed afterdepolarizations (DADs) induced by isoproterenol. METHODS AND RESULTS: Isolated patch-clamped guinea pig ventricular myocytes, loaded with fluo-3 acetoxymethyl ester (fluo-3 AM), were paced at 0.1 to 2 Hz. Isoproterenol (100 nmol/L) caused alterations in both phase 2 and phase 4 of the action potential (AP), consistent with EADs and DADs, respectively. During EADs (n = 16), similar to driven APs, increases in [Ca2+]i occurred simultaneously throughout the cell, whereas during DADs (n = 25), they originated in discrete cell sites and propagated as a wave. This difference was confirmed by analysis of eight EADs and DADs coupled to the same beat. Ca2+ transient linked to EADs reached a peak relative fluorescence level (expressed as percentage of the maximal level reached during the last stimulated beat) that was always higher than that reached during the DADs (77 +/- 3% versus 64 +/- 2%, P < .001). Spatial heterogeneity of Ca2+ transients was assessed by the maximal time interval between peaks monitored in different cell regions; this time lag was always greater during DADs than during EADs (290 versus 40 milliseconds, P = .006). CONCLUSIONS: The present study had two main findings. First, even very modest notches occurring during the plateau of the AP may be accompanied by a marked secondary increase in [Ca2+]i. Second, these Ca2+ transients occurring during EADs are synchronous throughout the cell and differ significantly from those observed under identical conditions during DADs.

Aniline Compounds↗
PubMed1995

Novel methods for the determination of the angiogenic activity of human tumors.

At present the most used method to quantify tumor angiogenesis in human solid tumors is the count of intratumoral microvessels in the primary lesion. This method requires the use of specific markers to vascular endothelium and of immunohistochemical procedures to visualize microvessels. Several studies have found that intratumoral microvessel density (IMD) determined in the primary tumor is significantly associated with metastasis and prognosis in some solid neoplasia, particularly in operable breast carcinoma. The subjective evaluation of IMD made by two observers at the microscope is rapid and of low cost, but presents some difficulties, mainly the identification of the most vascularized area ("hot-spot") within each tumor. This method can be improved upon to attain a better reproducibility among different pathologists. For example, the use of a multiparametric computerized image analysis system (CIAS) seems to be a promising tool to improve accuracy, feasibility and reproducibility of microvessel counts, although there are still some open technical problems to completely automate its use. Angiogenic activity is the result of a balance between angiogenic stimuli and angio-inhibition. Therefore the determination of angiogenic peptides and/or natural angiogenesis inhibitors in the tumor tissue, serum, or urine of cancer patients seems to be a promising alternative to microvessel counting. At present it is possible to determine the expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and transforming growth factor beta using immunohistochemical methods. Serum and urine levels of bFGF can be assessed using an immunoenzymatic assay. Methods used to assess the expression and levels of urokinase-type plasminogen activator (uPA) or plasminogen activator inhibitor-1 (PAI-1) have also been developed, and correlate with angiogenic activity and prognosis of patients with breast cancer. Finally, some investigational methods to assess angiogenesis in vivo are presented and discussed. Angiogenesis is a very complex phenomenon. Thus it seems reasonable to hypothesize that its assessment by using concurrently several of the available methods may provide more valid, accurate, and comprehensive information on the angiogenic activity of each single tumor. For a reliable and reproducible assessment of angiogenesis for all of the assays, validation procedures and quality control protocols are mandatory.

Breast Neoplasms↗