Adipose tissue: a new target for electroporation-enhanced DNA vaccines.

DNA vaccines delivered using electroporation (EP) have had clinical success, but these EP methods generally utilize invasive needle electrodes. Here, we demonstrate the delivery and immunogenicity of a DNA vaccine into subcutaneous adipose tissue cells using noninvasive EP. Using finite element analysis, we predicted that plate electrodes, when oriented properly, could effectively concentrate the electric field within adipose tissue. In practice, these electrodes generated widespread gene expression persisting for at least 60 days in vivo within interscapular subcutaneous fat pads of guinea pigs. We then applied this adipose-EP protocol to deliver a DNA vaccine coding for an influenza antigen into guinea pigs. The resulting host immune responses elicited were of a similar magnitude to those achieved by skin delivery with EP. The onset of the humoral immune response was more rapid when the DNA dose was spread over multiple injection sites, and increasing the voltage of the EP device increased the magnitude of the immune response. This study supports further development of EP protocols delivering gene-based therapies to subcutaneous fat.

Using computer and internet-based resources to teach health care planning and administration in an undergraduate medical program.

OBJECTIVE: We describe the teaching methods, involving computer and Internet-based resources, used in the "Administration and Planning in Health Care" course of the undergraduate medical program at the Federal University of Rio Grande do Sul. METHOD: Description on how the curriculum guidelines for the undergraduate medical education in Brazil have been implemented at this university. The guidelines specify that graduates should be skilled and knowledgeable in health care administration and management, understand the market dynamics of health care services, and be prepared to contribute to the development of health policy. RESULTS: A required 60-hour course provides students with an opportunity to learn about the structure, planning and administration of the Brazilian and of other health care systems, and their roles, as health care professionals, within those systems. The course is also intended to allow students to develop the minimal skill set required for manipulation of health care data available from national and international databases, and to use the Internet as a source of information in health care. The curriculum includes: Module 1 - basic computer skills, an introduction to networks as an infrastructure for management, the use of spreadsheets and databases for data processing and system modelling, retrieval of Internet-based health data and on-line bibliographic searches; Module 2 - health system financing and service quality management, using a university hospital as a case study; and Module 3 - a comparison of the Brazilian public health care system (SUS) with other national health systems resulting in a term paper formatted for journal submission and presented at a simulated conference at the end of the course. CONCLUSION: Progressive shift in emphasis from theory to practice in this course has resulted in better development of the skill set required for the students.

Hippocampal sclerosis revisited.

Studies dating back more than 150 years reported a relationship between hippocampal sclerosis and epilepsy. Retrospective studies of patients who underwent temporal lobectomy for intractable partial epilepsy found a relationship between a history of early childhood convulsions, hippocampal sclerosis, and the development of temporal lobe epilepsy. Many believe that febrile seizures lead to hippocampal damage and this in turn predisposes the patient to the development of temporal lobe epilepsy. Studies in adult rats have shown that seizures can lead to hippocampal damage and unprovoked recurrent seizures. However, many questions remain as to the relevance of early childhood seizures to hippocampal sclerosis and temporal lobe epilepsy. Human prospective epidemiologic studies have not shown a relationship between early childhood seizures and temporal lobe epilepsy. Recent MRI studies in humans suggest that a preexisting hippocampal lesion may predispose infants to experience febrile seizures, later on hippocampal sclerosis, and possibly temporal lobe epilepsy may occur. Unlike the studies in adult rats, normal immature rats with seizures have not been shown to develop hippocampal damage or unprovoked seizures in adulthood. Furthermore, animal studies reveal that preexisting brain abnormalities can predispose to hippocampal damage following seizures early in life. This paper reviews evidence for and against the view that early childhood convulsions, hippocampal sclerosis, and temporal lobe epilepsy are related, while also exploring clinical and animal studies on how seizures can lead to hippocampal damage, and how this can result in temporal lobe epilepsy. By better understanding the cause and effect relationship between early childhood seizures and hippocampal injury in normal and abnormal brains specific treatments can be developed that target the pathogenesis of epilepsy.

Digital diagnostic imaging with a comprehensive PACS: hypothetical economic evaluation at a large community hospital.

Since 1983, the 422-bed Victoria General Hospital (VGH) and Siemens Electric Limited have been piloting the implementation of digital medical imaging, including digital acquisition of diagnostic images, in British Columbia. Although full PACS is not yet in place at VGH, experience to date has been used to project annual cost figures (including capital replacement) for a fully digital department. The resulting economic evaluation has been labeled hypothetical to emphasize that some key cost components were estimated rather than observed; this paper presents updated cost figures based on recent revisions to proposed departmental equipment configuration. Compared with conventional diagnostic imaging, digital imaging appears to raise overall annual costs at VGH by nearly $0.7 million, (Canadian currency) or 11.6%; this is more favorable than the previous results, which indicated extra annual costs of $1 million (16.9%). Sensitivity analysis still indicates that all reasonable changes in the underlying assumptions result in higher costs for digital imaging than for conventional imaging. Digital imaging appears likely to offer lower radiation exposure to patients, shorter waiting times, and other potential advantages, but as yet the price of obtaining these benefits remains substantial.

Digital chest imaging using a 57-cm image intensifier: a receiver-operating characteristic study of user performance.

Chest radiography provides one of the great challenges to digital diagnostic imaging because of (1) the relatively large size of the chest field, (2) the contrast range required to resolve subtle pathological changes in soft tissue density, and (3) the high degree of spatial resolution required to discriminate pathological detail. The field size problem was resolved by using a 57-cm image intensifier whose video output of the chest could be digitized. The issue of contrast resolution was addressed in a recently completed receiver-operating characteristic study of the detectability of low-contrast densities in a humanoid chest phantom. The latter indicated that, despite the smaller size of the digital image, they were adequate for resolving clinically significant soft-tissue densities. The question of spatial resolution in digital diagnostic images is addressed in the study presented. A set of 41 clinical cases were selected to provide the typical range of diagnostic type experienced in routine diagnostic radiology. The images were each presented as conventional film, digital laser-printer, and digital video images. The results of an ROC analysis of five readers' performance in each of the viewing modes is presented.

Impact of image size on effectiveness of digital imaging systems.

Radiologists detect small diagnostic signals in radiographic film images by altering the distance between the eye and the image, effectively zooming in on a particular detail. Details thus enlarged are more perceptible to the viewer. Considering that conventional film images are nearly life-size, the potential for increasing the detection of small signals in this manner is high. Digital images, however, presented in video format are usually smaller than life-size, sometimes more than 50% smaller. While local enlargements using computer-based imaging systems are extremely useful, the radiologist cannot examine a whole, life-size image. The importance of the latter in the diagnostic process is revealed in detection studies using the same images of a chest phantom with small nodular inclusions, in different size formats. A clear positive correlation exists between overall image size and the detection of signals that are of a diagnostically-relevant size. While it is widely accepted that image fidelity is an important determinant in the clinical acceptability of digital radiography, digital image displays should also be large enough to display life-size images.

Signal detection in digital chest-phantom images acquired with an image intensifier.

Signal detection performance was evaluated on the basis of ROC analysis using both digital and conventional images of a humanoid chest phantom. Simulated focal (coin) lesions were the target pathology. Digital images were acquired using a 57-cm image intensifier, digitized to 1024 x 1024 x 10 bits, and compared, in both video and laser-printed film formats, with conventional 14 x 17-inch chest films. Signal detection using digital video and laser printed images, of the same image polarity as conventional images, was found not to differ significantly from that achieved using conventional images, despite the smaller size of the digital images.

Transbilayer movement of 24Na in sonicated phosphatidylcholine vesicles exposed to frequency-modulated microwave radiation.

Sonicated egg phosphatidylcholine vesicles loaded with 24Na+ were exposed at 20mW to a frequency-modulated (3 Hz) microwave field in the range of 2350 to 2550 MHz, or at 80 mW to a 2450-MHz CW (continuous wave) field, in a waveguide. The vesicle suspension absorbed microwaves at about 1 mW/ml and 25 mW/ml (CW experiment). The average temperature change of the irradiated suspension was less than 0.1 degree C from ambient. Leakage of 24Na+ from the vesicles for up to 19 hours was measured. No difference was noted in the movement of 24Na+ from the vesicles in the irradiated and control dispersions.