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[Cooling shell in renal transplantation. Thermometric evaluation of a prototype].

We have developed a cooling system for renal transplants designed to eliminate the second period of warm ischaemia corresponding to the vascular anastomosis phase of renal transplantation. This is an autonomous and independent system which forms a shell around the transplant. Following application of the system, cooling is achieved by refrigeration of a Multitherm sponge contained in the wall of the shell. The thermometric characteristics of a prototype were evaluated in vitro and in vivo in pigs. This system allows the kidney to be preserved at a temperature of less than 10 degrees C for 1 hour without inducing any risk of lesions of the renal surface. Human applications should be developed in the near future.

Anastomosis, Surgical↗

[The prototype of an expert system for the diagnosis of pseudotumorous lesions and tumors of the jaws: ADAPT-M. Archiviazione e Diagnosi Automatica di Pseudotumori e Tumori delle ossa Mascellari].

Many different tumors and pseudotumors may affect the jaw bones. The number and the rarity of most of these lesions, however, make both classification and differential diagnosis quite difficult. Computer software for statistical calculations and logical-deductive reasoning on vast amounts of data can improve diagnostic skills. These applications are defined as computer-assisted decision-making, medical decision support, or expert systems. This study was aimed at developing a prototype probabilistic expert system, based upon knowledge from an "ad hoc"computerized data base, as an aid in the radiologic diagnosis of jaw tumors and pseudotumors. This program has been called ADAPT-M. The study considered 92 patients with benign space-occupying and fully documented lesions of the jaw bones. For each case, a list of parameters concerning different radiologic exams was considered. From all these pieces of information a data base was built, to calculate both the prevalence of each type of lesion and the frequency of many variables in the single conditions. For each kind of lesion 44 variables were considered. ADAPT-M used a formula based on Bayes' theorem to calculate the "a posteriori" probability of a diagnosis in the presence of a symptom. Overall diagnostic probability rate was high when the highest score hypothesis was matched with pathologic findings (80%) and even higher (96.1%) when the two most probable diagnoses were considered together. As expected, ADAPT-M had higher sensitivity when used with lesions with typical semiology. This results in an unquestionable limitation, especially in the patients in whom a predictive diagnosis would be most desirable. The creation of a larger data base of known cases and software development may help increase the diagnostic accuracy of the ADAPT-M system.

Databases, Factual↗

A prototype Internet autopsy database. 1625 consecutive fetal and neonatal autopsy facesheets spanning 20 years.

OBJECTIVE: To demonstrate that cause-of-death statements can be generated by a computer algorithm from an autopsy database composed of diagnostic terms. DATA SOURCES: Over 49 000 autopsy facesheets contributed by over a dozen institutions were collected from a publicly accessible Internet autopsy database. This database is available at the following web site: http:@www.med.jhu.edu/pathology/iad.html STUDY SELECTION: To test the feasibility of creating and using a publicly available autopsy database, and to identify the technical and medicolegal problems that may arise with such a novel resource, a prototype study was designed by selecting autopsy facesheets from fetal and neonatal deaths. An algorithm was developed to determine the cause of death from the listing of anatomic diagnoses. DATA EXTRACTION: One thousand six hundred twenty-five fetal and neonatal autopsy facesheets were selected encompassing fetal and neonatal deaths occurring up to 28 days after birth. DATA SYNTHESIS: The algorithm determined causes of death from autopsy facesheet data in all cases. On review by an experienced pediatric pathologist, these automatically generated cause-of-death statements required no modification or only slight modification in over 90% of cases. CONCLUSIONS: A large multi-institutional autopsy database composed of demographic and diagnostic information has been deposited on the Internet. This information can be freely downloaded and used by any researcher without violating patient confidentiality. As a demonstration of one possible application of the database, fetal and neonatal autopsies generated cause-of-death statements using a computer algorithm. One can anticipate that the wealth of information contained in autopsy facesheets can be assembled into a database that will serve the public interest.

Algorithms↗

Identifying family violence: a community prototype incorporating Native Hawaiian values and practices.

The manual, Identifying Family Violence: A Community Prototype Incorporating Native Hawaiian Values and Practices is a pioneering effort which health care professionals can adapt, expand, or refine in their work with Hawaiians and non-Hawaiians as well. Our assumption is that a culturally integrated approach is a necessary component of a community's strategy to address this escalating problem. Family violence is a virus which threatens all of us. It weakens the pohai ke aloha (circle of aloha) which binds the family together. When the pohai ke aloha is weakened, each family member's mana (vital force) declines. When a familys mana is in decline, the lokahi (harmony) within the family and our community is disrupted. We, as a community, a society, a nation, cannot afford to stand by and condone violence within the family. Ultimately, we all suffer when our families are hurting. Hana pono ka puuwai malamalama.. An enlightened heart acts accordingly.

Cultural Diversity↗

The PEN&PAD data entry system: from prototype to practical system.

This paper describes some of the issues addressed in the transition of the PEN&PAD from prototype clinical workstation to practical data entry system for use by general practitioners in the UK. Background and motivation of the PEN&PAD and GALEN projects are presented before the operation of the PEN&PAD user interface is described. A number of issues which have arisen in the development of the PEN&PAD Data Entry System are discussed.

Humans↗

Just tell me what you want!: the promise and perils of rapid prototyping with the World Wide Web.

Construction of applications using the World Wide Web architecture and Hypertext Markup Language (HTML) documents is relatively simple. We are exploring this approach with an application, called PolyMed now in use by surgical residents for one year. We monitored use and obtained user feedback to develop new features and eliminate undesirable ones. The system has been used to keep track of over 4,200 patients. We predicted, several advantages and disadvantages to this approach to prototyping clinical applications. Our experience confirms some advantages (ease of development and customization, ability to exploit non-Web system components, and simplified user interface design) and disadvantages (lack of database management services). Some predicted disadvantages failed to materialize (difficulty modeling a clinical application with hypertext and inconveniences associated with the "connectionless" nature of the Web). We were disappointed to find that while integration of external Web applications (such as Medline) into our application was easy, our users did not find it useful.

Attitude to Computers↗

The in vivo effects of a prototype diode laser coagulator/vaporizing endoprobe used to perform retinectomy and retinotomy in rabbits.

BACKGROUND AND OBJECTIVE: A pilot study was conducted to evaluate the use of a prototype intraocular carbon-coated diode laser probe for performing single-instrument internal retinotomy and retinectomy. MATERIALS AND METHODS: A 20-gauge endolaser probe was used to perform retinotomies on 10 anesthetized rabbits. Two protocols were examined: one using low power and long duration, and one using high power and short duration. Retinotomies were performed on attached and experimentally detached retinas. RESULTS: Retinotomies were performed in all eyes using both protocols. The edges had photocoagulative effects in all cases. The eyes treated with the longer duration, lower power protocol had scleral damage, whereas the eyes treated with shorter duration, higher power did not. CONCLUSION: Although the diode laser coagulator/cutter may be used for retinotomies, it should be studied further.

Animals↗

Rapid carcinogenicity testing system with transgenic mice harboring human prototype c-HRAS gene.

Rapid carcinogenicity tests were done with transgenic (Tg) mice human prototype c-HRAS gene, namely BALB/cByJ x C57BL/6JF1-TgN(HRAS)2 or CB6F1-HRAS2 mice. The studies were conducted as the first step in the evaluation of the CB6F1-HRAS2 mouse as a model for the rapid carcinogenicity testing system. Results of short-term tests of various genotoxic carcinogens indicated that CB6F1-HRAS2 mice are more susceptible to these carcinogens than control non-Tg mice. According to the first-step evaluation studies, more rapid onset and a higher incidence of more malignant tumors can be expected with a higher probability after treatment with various genotoxic carcinogens in the CB6F1-HRAS2 mice than in control non-Tg mice. The CB6F1-HRAS2 mouse seems to be a promising candidate as an animal model for the development of a rapid carcinogenicity testing system.

Animals↗

Assessment of a prototype battery operated wax-knife for domiciliary and surgery use.

The aims of this study were to examine a prototype battery operated wax-knife, assess the extent to which manufacturer's claims have been achieved and determine its potential for clinical use. The mean time required for the wax-knife to achieve an operating temperature of 150 degrees C was 20.2(+/-4.3) s. The mean operating temperature of the ceramic blade was 155.4(+/-3.9) degrees C, range 150 degrees C to 162 degrees C. The mean usage time following full battery recharge was 42 (+/-2) minutes. The wax-knife provided a direct heating tool which retained many of the characteristics of the traditional wax-knife and was suitable for use in the surgery and in domiciliary situations.

Burns↗

Rapid prototyping techniques for anatomical modelling in medicine.

The rapid advances in computer technology, often driven by the demands of industry, have created new possibilities in surgery which previous generations of surgeons could only have imagined. Improved imaging with computerised tomography (CT) has been followed by magnetic resonance imaging (MRI) and, more recently, it has become possible to reformat the data as three-dimensional images. Computer technology has new moved forward with the advent of rapid prototyping techniques (RPT) which allow both the production of models of the hard tissues and custom-made prostheses from computerised scanning data. In this article we review the development and current technologies available in RPT and the applications of this advance in surgery and illustrate this with two case reports.

Child↗

Assessing the accuracy of a prototype drill guide for fibular graft placement in femoral head necrosis.

A prototype drill guide was developed to improve the accuracy of surgical placement of fibular grafts for the treatment of femoral head necrosis. To document performance, two tantalum beads, one placed on the lateral femoral shaft and the other embedded in the superior portion of the head, were used to define the desired graft tract in a series of seven surrogate femurs. Two orthogonal x-rays of the drill guide mounted on each surrogate femur were taken both before and after drilling. After stylus digitization of each x-ray pair, a computer program calculated the achieved accuracy of the drill. The mean of the absolute error between the desired versus obtained position of the drill tip was 3.68 mm (s.d. 1.24 mm), and the random component of the error was 1.98 mm (s.d. 0.89 mm).

Anthropometry↗

A potent and selective CGRP2 agonist, [Cys(Et)2,7]hCGRP alpha: comparison in prototypical CGRP1 and CGRP2 in vitro bioassays.

The development of highly selective and potent agonists and antagonists is critical in evaluating the physiological role(s) of each receptor subtype in a peptide family. The existence of at least two calcitonin gene related peptide (CGRP) receptor subtypes has been proposed based on the potency of CGRP8-37 to antagonize the effect of hCGRP alpha in the guinea pig atrium and the agonistic properties of the linear analogue [Cys(Acm)2,7]hCGRP alpha to mimic the effect of hCGRP alpha in the rat vas deferens. However, the rather low potency of [Cys(Acm)2,7]hCGRP alpha (ED50 = 82 +/- 7.5 nM) to activate the CGRP2 receptor subtype limits its usefulness. Accordingly, we investigated various structural modifications of this linear analogue in prototypical CGRP1 and CGRP2 in vitro bioassays. Among them, replacing the acetaminomethyl moiety (Acm) by an ethylamide group, [Cys(Et)2,7]hCGRP alpha demonstrated a high potency to inhibit the rat vas deferens twitch response (ED50 = 3.4 +/- 1.2 nM), whereas in the guinea pig atrium, this analogue induced only a slight inotropic effect at very high concentrations (1 microM). Moreover, [Cys(Et)2,7]hCGRP alpha as well as the addition of a tyrosine residue at the N-terminal, [Tyr0,Cys(Et)2,7]hCGRP alpha, competed with high affinities for [125I]hCGRP binding in rat brain homogenates (IC50 = 0.3 and 0.1 nM, respectively). Taken together, these results suggest that [Cys(Et)2,7]hCGRP alpha is a new potent analogue that could prove valuable in addressing the functional relevance of the CGRP2 receptor class.

Animals↗

Automatic annotation for biological sequences by extraction of keywords from MEDLINE abstracts. Development of a prototype system.

We have developed a prototype for the automatic annotation of functional characteristics in protein families. The system is able to extract biological information directly from scientific literature in the form of MEDLINE abstracts. The criterion for selecting relevant keywords is the difference between their frequency in the abstracts associated with the protein family under study and its frequency in other unrelated protein families. The concept of functional information associated to protein families is the key feature of our system and gathers evolutionary information into the problem of functional annotation of biological sequences. The system has been tested in two different scenarios: first, a large set of protein families with a small number of abstract per family and second, selected protein families with large number of abstracts attached to each one. In both cases the performances are compared with annotations provided by human experts showing a clear relation between the amount of information provided to the system and the quality of the annotations. The automatic annotations are in many cases of similar quality to the ones contained in current data bases. The possibilities and difficulties to be encountered during the development of a full system for automatic annotation are discussed.

Abstracting and Indexing↗

HyperCare: a prototype of an active database for compliance with essential hypertension therapy guidelines.

HyperCare is a prototype of a decision support system for essential hypertension care management. The medical knowledge implemented in HyperCare derives from the guidelines for the management of mild hypertension of the World Health Organization/International Society of Hypertension, and from the recommendations of the United States Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure. HyperCare has been implemented using Chimera, an active database language developed at the Politecnico di Milano. HyperCare proves the possibility to use active database systems in developing a medical data-intensive application where inferential elaboration of moderate complexity is required.

Databases as Topic↗

A prototype Web site for immunization knowledge maintenance.

IMM/Web is a prototype Web site designed to assist in the maintenance of the knowledge required to perform computer-based forecasting for childhood immunization. IMM/Web operates in conjunction with IMM/Serve, a immunization forecasting program that takes a child's immunization history and produces recommendations as to which vaccinations are due, and which should be scheduled next. IMM/Serve's domain knowledge is expressed in both tabular and rule-based form. Using IMM/Web, the various tabular forecasting parameters can be modified via the Web. Test cases can then be generated automatically which can be used to help verify the new version of logic. Finally, the test cases can be automatically passed for IMM/Serve to analyze using the newly defined parameters. The IMM/Web project is exploring how the process of updating, customizing, and testing new versions of a computer-based clinical guideline might be performed and guided in an organized fashion via the World-Wide Web.

Child↗

Development of a custom designed TAH using rapid prototyping.

The failure of the orthotopic implantation of a totally implantable artificial heart (TAH) was due mainly to anatomic mismatches in the conduits of the conventional TAH system. To overcome this anatomic incompatibility, a custom design and fabrication process was designed using the rapid prototyping (RP) technique. After three dimensional reconstruction of magnetic resonance imaging of the thoracic cavity and vascular remnants of the recipient, study of anatomic fit was done using the reconstructed thoracic model and three dimensional computer aided design (CAD) model. The direction of the inflow and outflow conduits of the blood sac was changed with a Unigraphics CAD. The RP model of the designed chamber was fabricated and examined for anatomic compatibility. Through this approach, the minute directional mismatch of the inflow and outflow conduits was improved. Thus, a new custom designed moving actuator Korean TAH with CAD and RP techniques was developed.

Biomedical Engineering↗

Bispecific monoclonal antibody complexes facilitate erythrocyte binding and liver clearance of a prototype particulate pathogen in a monkey model.

We used Anger camera imaging in a monkey model to investigate the organ localization of a prototype particulate pathogen, 131I-labeled bacteriophage phi X174, after it was bound to the primate erythrocyte complement receptor and then cleared from the circulation. This 131I-labeled phi X174 was infused into the circulation of an immunized monkey, and the nascently formed immune complexes showed rapid and quantitative binding to erythrocytes via the immune adherence reaction (complement-mediated binding). Alternatively, phi X174 was infused into the circulation of a naive animal, and then cross-linked bispecific mAb complexes (heteropolymers, anti-CR1 x anti-phi X174) were infused into the circulation. The infused heteropolymers also facilitated rapid and quantitative binding of phi X174 to erythrocytes. In both cases, after a short lag period, the erythrocyte-bound phi X174 was rapidly cleared from the circulation, and the vast majority of the radiolabel was cleared to the liver, with a small amount clearing to the spleen. Further liver imaging confirmed that within 24 h most of the bacteriophage previously cleared to the liver via the heteropolymer system was phagocytosed and destroyed. The findings in this model system provide additional evidence for the potential utility of heteropolymers to facilitate the safe and rapid clearance of blood-borne pathogens as a potential treatment for infectious diseases.

Animals↗

The prototypic Th2 autoimmunity induced by mercury is dependent on IFN-gamma and not Th1/Th2 imbalance.

Imbalances of Th1- and Th2-type responses have been postulated to be a predisposing factor for both humoral and cellular mediated autoimmune diseases. To further define their roles in systemic autoimmunity, IL-4 and IFN-gamma gene knockout mice were studied for susceptibility to the prototypic Th2-mediated mercury-induced autoimmunity. A predominant Th2-type response following HgCl2 treatment of wild-type B10.S mice was confirmed by the findings of a significant increase in splenic IL-4 and hypergammaglobulinemia primarily of the IgG1 isotype, without an increase in IFN-gamma levels. Paradoxically, IL-4-deficient mice developed the characteristic anti-nucleolar autoantibodies and tissue deposition of immune complexes, while IFN-gamma-deficient mice had very low autoantibody levels and essentially normal immunohistology. Studies to define defects in Ab responses of IFN-gamma-deficient mice, using the T-dependent Ag (4-hydroxy-3-nitrophenyl)acetyl, revealed an attenuated IgG response to low and to a lesser extent high doses of (4-hydroxy-3-nitrophenyl)acetyl-hemocyanin, but maintenance of affinity maturation. These results indicate that Th1/Th2 imbalance does not directly play a role in susceptibility to mercury-induced autoimmunity, and suggest that the dependence on Th1-type responses in certain autoimmune diseases is due to the requirement for IFN-gamma for Ab production to weakly antigenic self molecules.

Animals↗