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At least 973 records · Page 54Linked to original sources
PubMed2001

Prototype percutaneous thrombolytic device: preclinical testing in subacute inferior vena caval thrombosis in a pig model.

PURPOSE: To develop an animal model of subacute inferior vena caval (IVC) thrombosis and apply this model in evaluating the safety and efficacy of a prototype percutaneous thrombolytic device for restoring patency. MATERIALS AND METHODS: In 11 pigs, a stent with a ligature in the middle was placed in the IVC. Thrombin was injected to induce thrombosis. Hemostasis was achieved by using an occlusion balloon. The stent was ligated to prevent thrombus migration. Five to 8 days after thrombus induction, the ligature was broken and the stent fully deployed. In 10 animals, thrombectomy was performed by using the percutaneous thrombolytic device. A vena caval filter was inserted at the beginning of each declotting procedure. Thrombus removal percentage was estimated and pulmonary angiograms obtained to detect embolism before and after thrombectomy. The IVC was analyzed histologically. To determine thrombus composition, one animal was sacrificed without thrombectomy. Concerning procedural safety, failure of the stent delivery system, stent migration, and venous perforation due to balloon inflation and the stent placement or thrombectomy procedure were evaluated. RESULTS: Thrombus creation was successful in all animals. Fragmentation led to 75%--100% thrombus removal with flow restoration in all cases. There were no episodes of stent delivery failure, stent migration, or venous perforation. No significant pulmonary embolism was observed. In one case, a vessel dissection was identified at histologic examination. CONCLUSION: In this animal model of IVC thrombosis, the percutaneous thrombolytic device is effective and safe for clot removal.

Animals↗
PubMed2005

Pooling samples within microarray studies: a comparative analysis of rat liver transcription response to prototypical toxicants.

Combining or pooling individual samples when carrying out transcript profiling using microarrays is a fairly common means to reduce both the cost and complexity of data analysis. However, pooling does not allow for statistical comparison of changes between samples and can result in a loss of information. Because a rigorous comparison of the identified expression changes from the two approaches has not been reported, we compared the results for hepatic transcript profiles from pooled vs. individual samples. Hepatic transcript profiles from a single-dose time-course rat study in response to the prototypical toxicants clofibrate, diethylhexylphthalate, and valproic acid were evaluated. Approximately 50% more transcript expression changes were observed in the individual (statistical) analysis compared with the pooled analysis. While the majority of these changes were less than twofold in magnitude ( approximately 80%), a substantial number were greater than twofold (approximately 20%). Transcript changes unique to the individual analysis were confirmed by quantitative RT-PCR, while all the changes unique to the pooled analysis did not confirm. The individual analysis identified more hits per biological pathway than the pooled approach. Many of the transcripts identified by the individual analysis were novel findings and may contribute to a better understanding of molecular mechanisms of these compounds. Furthermore, having individual animal data provided the opportunity to correlate changes in transcript expression to phenotypes (i.e., histology) observed in toxicology studies. The two approaches were similar when clustering methods were used despite the large difference in the absolute number of transcripts changed. In summary, pooling reduced resource requirements substantially, but the individual approach enabled statistical analysis that identified more gene expression changes to evaluate mechanisms of toxicity. An individual animal approach becomes more valuable when the overall expression response is subtle and/or when associating expression data to variable phenotypic responses.

Animals↗
PubMed2005

Treatment of human tumor xenografts with monoclonal antibody 806 in combination with a prototypical epidermal growth factor receptor-specific antibody generates enhanced antitumor activity.

Monoclonal antibody (mAb) 806 is a novel epidermal growth factor receptor (EGFR) antibody with significant antitumor activity that recognizes a mutant EGFR commonly expressed in glioma known as delta2-7 EGFR (de2-7 EGFR or EGFRvIII) and a subset of the wild-type (wt) EGFR found in cells that overexpress the receptor. We have used two human xenograft mouse models to examine the efficacy of mAb 806 in combination with mAb 528, a prototypical anti-EGFR antibody with similar specificity to cetuximab. Treatment of nude mice, bearing s.c. or i.c. tumor human xenografts expressing the wt or de2-7 EGFR, with mAbs 806 and 528 in combination resulted in additive and in some cases synergistic, antitumor activity. Interestingly, mAb 528 was also effective against xenografts expressing the ligand independent de2-7 EGFR when used as a single agent, showing that its antitumor activity is not merely mediated through inhibition of ligand binding. When used as single agents, neither mAbs 806 or 528 induced down-regulation of the de2-7 EGFR either in vitro or in vivo. In contrast, the combination of antibodies produced a rapid and dramatic decrease in the total cell surface de2-7 EGFR both in vitro and in xenografts. Consistent with this decrease in total cell surface de2-7 EGFR, we observed up-regulation of the cell cycle inhibitor p27(KIP1) and a decrease in tumor cell proliferation as measured by Ki-67 immunostaining when the antibodies were used in combination in vivo. Thus, mAb 806 can synergize with other EGFR-specific antibodies thereby providing a rationale for its translation into the clinic.

Animals↗
PubMed1999

Interactive image-guided surgery system with high-performance computing capabilities on low-cost workstations: a prototype.

We present a new frameless stereotatic system prototype that has been initially validated in functional neurosurgery operations and that makes use of an optical position tracker for image-guided neurosurgery. Several devices for tracking different surgical instruments have been designed and manufactured. These devices include an array of infrared light-emitting diodes that are tracked by three charge-coupled device cameras. The system presents several new approaches for surgery planning. For high-quality 3D images of the patient's anatomy, we have developed a parallel version of a volume-rendering algorithm, thus enabling real-time 3D anatomy manipulation on low-cost PC workstations. In order to test the accuracy of the system, the localization of the target by means of a stereotatic frame has been compared with frameless techniques, obtaining a difference of about 1 +/- 1 mm.

Algorithms↗
PubMedDate not supplied

The ascidian dihydropyridine-resistant calcium channel as the prototype of chordate L-type calcium channel.

This review describes recent findings on voltage-gated Ca channel (Cav channel) cloned from ascidians, the most primitive chordates. Ascidian L-type like Cav channel has several unusual features: (1). it is closely related to the prototype of chordate L-type Cav channels by sequence alignment; (2). it is resistant to dihydropyridine due to single amino acid change in the pore region, and (3). maternally provided RNA putatively encodes a truncated protein which has remarkable suppressive effect on Cav channel expression during development. Ascidian Cav channel will provide a useful molecular clue in the future to understand Ca(2+)-regulated cell differentiation and physiology with the background of recently defined ascidian genome and molecular biological tools.

Amino Acid Sequence↗
PubMedDate not supplied

Categories, dimensions and prototypes: critical issues for psychiatric classification.

Being descendants of the Kraepelinian nosology, DSM-IV and ICD-10 rely largely on the internal cohesion of the clinical picture and the pattern of course and outcome as validating criteria of the definitions of mental disorders. The majority of the research diagnostic criteria are provisional and should be extensively tested against empirical evidence. The crucial issue is whether psychiatric disorders, as currently defined in DSM-IV and ICD-10, are clearly separated from one another and from normality. Options for future revisions of the classifications include categorical typologies, dimensional models and empirically derived prototypes. The advantages and disadvantages of each option are outlined, highlighting the need for new research focusing on these critical issues.

Diagnosis, Differential↗
PubMed2006

Clinical effect of 'pure' heart rate slowing with a prototype If current inhibitor: placebo-controlled experience with ivabradine.

Heart rate slowing is generally accepted as effective for angina prevention but this approach has not been rigorously evaluated as no pure heart rate slowing treatment has been available. With the identification of the I(f) current, the primary modulator of heart rate, and use of this as a target for drug development, the role of isolated heart rate slowing can be elucidated. More than 4,000 patients now have been studied in angina prevention trials with ivabradine, a prototype I(f) current inhibitor devoid of other cardiovascular effects. These studies demonstrate the efficacy of isolated heart rate slowing for angina prevention. Indeed, in one direct comparison with atenolol involving 939 patients, ivabradine not only was non inferior to the Beta-blocker but nominally appeared to be more efficient in angina prevention. Moreover, since ivabradine is devoid of most of the adverse effects of beta-blockers (and of calcium channel blockers), it is a suitable alternative when these established drugs are not adequately tolerated. Additional studies now must assess other potential actions in patients with coronary disease.

Angina Pectoris↗
PubMed1990

A prototype medical workstation for computer-assisted stereotactic neurosurgery.

We have developed a prototype display workstation for use in stereotactic neurosurgery. Patient image data from computed tomography, magnetic resonance imaging, and digital subtraction angiography are acquired with the stereotactic frame in place and subsequently transferred to the workstation for further processing. Target points may be identified on any image type and probe trajectories defined. Any point or line indicated on one set of images may be transferred immediately to other images, to determine, for instance, safe avascular probe paths. We present some general outlines for the use of computers for stereotactic neurosurgery and discuss the different components of the current system. Finally, we make some suggestions as to further developments.

Brain↗
PubMed1991

Biochemical and molecular aspects of late-onset GM2-gangliosidosis: B1 variant as a prototype.

Clinical phenotypes of GM2-gangliosidosis are complex. In the past 5 years it has become possible to dissect out the phenotypic complexity on the basis of abnormalities on the DNA level. Available data on the 18 disease-causing mutations so far identified in the beta-hexosaminidase alpha-gene allow an oversimplified generalization; mutations that produce no or highly unstable mRNA cause the most severe infantile forms of the disease, while all late-onset forms are due to point mutations within the protein-coding region, which generate stable mRNA and stable mutant protein. The mutation underlying the distinct phenotype of Jewish adult Tay-Sachs disease will be discussed separately by Navon. The prototype of juvenile Tay-Sachs disease is the B1 variant. The disease was first recognized by an apparent discrepancy in the beta-hexosaminidase activities toward the conventional artificial substrates and the natural lipid substrate, GM2-ganglioside. When assayed with the conventional artificial substrates, patients appear reasonably normal while they are severely deficient in hydrolysis of the natural substrate (and more recently the 'sulfated' artificial substrate). The majority of B1 patients fall in the clinical category of juvenile GM2-gangliosidosis. Some of the earlier juvenile patients reported to have partial hexosaminidase A deficiency are likely to be B1 variant. Two point mutations, occurring at a mutation hot spot, CpG, and both affecting the same codon, have been described as the causes of the B1 variant phenotype; G533----A, Arg178----His; and C532----T, Arg178----Cys. The latter mutation has been found so far only in one Czechoslovakian family. In contrast, the former mutation has a wide geographic and ethnic distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed2003

Localized neurotransmitter release for use in a prototype retinal interface.

PURPOSE: Current neural prostheses use electricity as the mode of stimulation, yet information transfer in neural circuitry is primarily through chemical transmitters. To address this disparity, this study was conducted to devise a prototype interface for a retinal prosthetic based on localized chemical delivery. The goal was to determine whether fluidic delivery through microfabricated apertures could be used to stimulate at single-cell dimensions. METHODS: A drug delivery system was microfabricated based on a 5- or 10- microm aperture in a 500-nm thick silicon nitride membrane to localize and limit transmitter release. The aperture overlies a microfluidic delivery channel in a silicone elastomer. To demonstrate the effectiveness of this transmitter-based prosthesis, rat pheochromocytoma cells (PC12 cell line) were grown on the surface of the device to test the precision of stimulation, using bradykinin as a stimulant and measuring fluorescence from the calcium indicator, fluo-4. RESULTS: The extent of stimulation could be controlled accurately by varying the concentration of stimulant, from a single cell adjacent to the aperture to a broad area of cells. The stimulation radius was as small as 10 microm, corresponding to stimulation volumes as small as 2 pL. The relationship between the extent of stimulation and concentration was linear. CONCLUSIONS: The demonstration of localized chemical stimulation of excitable cells illustrates the potential of this technology for retinal prostheses. Although this is only a proof of concept of neurotransmitter stimulation for a retinal prosthesis, it is a significant first step toward mimicking neurotransmitter release during synaptic transmission.

Aniline Compounds↗
PubMed2003

Reduction of postural sway by use of a vibrotactile balance prosthesis prototype in subjects with vestibular deficits.

To evaluate the effectiveness of a prototype vibrotactile balance prosthesis in maintaining balance during dynamic posturography, we studied 6 subjects with unilateral or bilateral vestibular deficit by means of Equitest computerized dynamic posturography (CDP). Their anterior-posterior (AP) sway at the small of the back was measured with a micromechanical rate gyroscope and a linear accelerometer. The resulting tilt estimate was displayed by a vibrotactile array attached to the torso. The vibration served as tilt feedback to the subject. Subject performance was evaluated with the tilt performance index (TPI), which is the inverse of the root-mean-square of tilt. We found that the balance prosthesis reduced the subjects' AP sway. The subjects' results without the balance prosthesis on CDP sensory organization tests (SOTs) 5 and 6 were compared to results with the prosthesis. The average TPI increased significantly (p < .05) when vibrotactile feedback was used as compared to the unaided condition. This finding was true for both SOTs 5 and 6. We conclude that vibrotactile feedback of estimated AP body tilt improved the subjects' ability to perform selected CDP tests. Some of the subjects were able to stand throughout the test with the device turned on, whereas they otherwise constantly fell.

Adult↗
PubMedDate not supplied

Moving diabetes management from clinic to community: development of a prototype based on automated voice messaging.

The purpose of this study is twofold. First, it provides a review of the literature supporting the development of a new service to help patients with diabetes and their providers manage their care. This service, automated voice messaging (AVM) with nurse follow-up, allows for systematic and intensive patient monitoring and diabetes education as well as a means of focusing clinical resources where they are most needed. Second, it provides a description of a prototype AVM-based diabetes management service that has been developed as part of two ongoing, randomized, controlled trials to test the efficacy of AVM care for patients with Type 2 diabetes. Preliminary findings from implementing this service in two large public healthcare systems suggest that AVM-supported care is feasible, desirable by clinicians and patients with diabetes, and may identify serious health problems that otherwise would go unnoted through standard means of clinic-based patient care.

Clinical Protocols↗
PubMedDate not supplied

Glomerulonephritis with fibrillary deposition in a transgenic mouse carrying the human prototype c-Ha-ras gene (rasH2 mouse).

Glomerulonephritis was observed in a 34-week-old transgenic CB6F1 mouse carrying the human prototype c-Ha-ras gene (rasH2 mouse) from a medium-term carcinogenicity study of N-methyl-N-nitrosourea (MNU). Lesions were characterized by severe diffuse enlargement and prominent hyalinization of glomeruli. The hyaline material was positive for periodic acid-Schiff but negative for amyloid by the Congo red method. Immunohistochemically, affected glomeruli were positive for polyclonal anti-mouse IgG. Ultrastructurally, there were characteristic subendothelial and mesangial deposits composed of fibrils showing a fingerprint pattern. Lamellae were 7.5-14.3 nm in diameter and formed multilayered structures. In addition to the renal lesions, a lymphoma was observed in the thymus, with metastasis to the spleen and some lymph nodes. However, there was no glomerulonephritis in 32 other mice bearing thymic lymphomas and in more than 40 males and females given MNU in the same study. Thus, the lesions in this mouse may have been spontaneous. Glomerulonephritis was not found in more than 120 other male and female rasH2 mice in our facility. This is the first report of glomerulonephritis in a rasH2 mouse, a promising candidate for medium-term carcinogenicity risk assessment.

Animals↗
PubMedDate not supplied

Pathological features of spontaneous and induced tumors in transgenic mice carrying a human prototype c-Ha-ras gene used for six-month carcinogenicity studies.

To validate the transgenic (Tg) mouse carrying a human prototype c-Ha-ras gene (rasH2 mouse) as a model for short or medium-term carcinogenicity testing, 6-mo carcinogenicity studies using more than 30 chemicals, including carcinogens and noncarcinogens, have been performed. The results obtained so far indicate that rasH2 mice are generally much more susceptible to both mutagenic and nonmutagenic carcinogens than are non-Tg mice, pointing to advantageous application for detection of carcinogenic potential. In this review, histopathological features and diagnostic criteria for spontaneous and induced-tumors observed in our 6-mo carcinogenicity studies are described. Incidences of spontaneous tumors were generally low in rasH2 mice during the 6-mo studies, although values for lung adenomas and splenic hemangiosarcomas were higher than those in the control non-Tg mice. A few forestomach papillomas and skin papillomas were also observed in the control rasH2 mice. The target organs in rasH2 mice treated with known carcinogens were not always identical to those in the treated B6C3F1 mice in 2-yr carcinogenicity bioassays, with forestomach squamous cell tumors, lung alveolar epithelial tumors and/or hemangiosarcomas in the spleen observed in addition to some but not all of the lesions in target organs observed in non-Tg mice in long-term carcinogenicity bioassays. The results of the present histological study suggest that the lung, spleen and/or forestomach, where tumors are induced in rasH2 mice treated with known carcinogens, should be regarded as informative target organs in addition to the target organs reported in previous long-term carcinogenicity bioassays in rats and mice.

Animals↗
PubMed1981

The effect of private attitudes on public policy. Prenatal screening for neural tube defects as a prototype.

The quantitative use of patients' attitudes in medicine has thus far been limited to decisions involving either treatment alternatives or the use or nonuse of a particular diagnostic test. Preference theory has not been applied either to the use of screening tests or to the development of large-scale health-related public policy decisions. In this paper we have, in a prototypical fashion, analyzed the effect patient attitudes have on a public policy decision faced by many countries today--whether or not to institute a screening program for neural tube defects. We have assessed the attitudes of 338 prospective parents toward many of the sequelae expected from the introduction, or lack thereof, of the alpha-fetoprotein screening program--induced abortion from amniocentesis, elective abortion, and the birth of a defective child. Using these data and information collected by the United Kingdom study on alpha-fetoprotein, we have estimated the proportion of patients coming to genetic counseling who would benefit from the availability of a screening program for neural tube defects.

Abortion, Spontaneous↗
PubMedDate not supplied

A prototype decision support system for differential diagnosis of psychotic, mood, and organic mental disorders.

The authors designed a decision support system to assist mental health professionals to perform differential diagnoses of psychotic, mood, and organic mental disorders in accordance with the American Psychiatric Association's revised third edition of the Diagnostic and Statistical Manual of Mental Disorders. A prototype system arrived at through a rigorous methodology illustrates a style of development that attempts to ensure system maintainability, correctness, and consistency of deduction and promotes high quality in software.

Decision Making, Computer-Assisted↗
PubMedDate not supplied

Prototype decision support system for a differential diagnosis of psychotic, mood, and organic mental disorders: Part II.

This paper presents a prototype parallel-processing decision support system, based on the ALICE graph reduction machine, for the differential diagnosis of psychotic, mood, and organic mental disorders in accordance with the American Psychiatric Association's revised third edition of the Diagnostic and Statistical Manual of Mental Disorders. The paper extends the authors' earlier work where the same domain was implemented on an expert-system shell using a rule-based representation.

Computer Graphics↗