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Screening guidelines for colorectal cancer.

Evidence-based guidelines recommend that all asymptomatic, average-risk U.S. citizens >50 years of age be encouraged to undergo screening for colorectal cancer. Those at higher risk should be offered more intensive screening and follow-up surveillance. It is estimated that widespread adoption of these recommendations could reduce mortality from colorectal cancer by >50%. The only screening methods that have been evaluated directly are the fecal occult blood test and flexible sigmoidoscopy. Current guidelines now recommend annual screening for fecal occult blood plus flexible sigmoidoscopy every 5 years for asymptomatic, average-risk men and women >50 years of age. Indirect evidence supports the options of colonoscopy or barium enema x-ray screening for highly motivated individuals, but these methods have not yet been tested in prospective trials. In the future, gene-based screening tests may be developed, and computed tomography of the colon ("virtual colonoscopy") may prove effective and feasible.

Age Factors↗

alpha1-Fetoprotein measurement in blood spotted on paper: discriminating test for hereditary tyrosinemia in neonatal mass screening.

We describe an electroimmunodiffusion technique for measuring alpha1-fetoprotein in blood spotted on chromatography paper. The system is being used as a complementary test in a neonatal mass-screening program for detection of inborn metabolic diseases in the Province of Quebec. In a series of 102 cases of neonatal hypertyrosinemia, the test has proven to be highly discriminative for hereditary tyrosinemia. It has permitted early detection of eight cases of this disease, including two that would have been missed by the previously used screening procedure, tyrosine measurement only. The test not only virtually eliminates the risk of misdiagnosis or missed diagnosis, but also permits earlier diagnosis of hereditary tyrosinemia and considerably reduces the follow-up work required for newborns with transitory tyrosinemia. The AFP test is simple, fast, practical, and inexpensive. Combined with tyrosine determination, it constitutes an optimal device for mass screening of hereditary tyrosinemia.

Amino Acid Metabolism, Inborn Errors↗

Using QuickTime virtual reality objects in computer-assisted instruction of gross anatomy: Yorick--the VR Skull.

QuickTime virtual reality (QTVR) is a software technology that creates, on a normal computer screen, the illusion of holding and turning a three-dimensional object. QTVR is a practical photo-realistic virtual reality technology that is easily implemented on any current personal computer or via the Internet with no special hardware requirements. Because of its ability to present dynamic photo-quality images, we reasoned that QTVR can provide a more realistic presentation of anatomic structure than two-dimensional atlas pictures and facilitate study of specimens outside the dissection lab. We created QTVR objects, using portions of the skull, and incorporated them into an instructional program for first-year medical students. To obtain images, the bones of the skull were mounted on a rotating table, and a digital camera was positioned on a swinging arm so that the focal point remained coincident with the rotational center of the object as the camera was panned through a vertical arc. Digital images were captured at intervals of 10 degrees rotation of the object (horizontal pan). The camera was then swung through an arc with additional horizontal pan sequences taken at 10 degrees intervals of vertical pan. The images were edited to place the object on a solid black background, then assembled into a linear QuickTime movie. The linear movie was processed to yield a QTVR object movie that can be manipulated on vertical and horizontal axes using the mouse. QTVR movies were incorporated into an interactive environment that provided labeling, links to text-based information and self-testing capabilities. This program, Yorick-the VR Skull, has been used in our first-year medical and graduate gross anatomy courses for the past two years. Results of student evaluation of the program indicate that this QTVR-based program is an effective learning tool that is well received by students.

Anatomy↗

[Screening for prevention of colorectal carcinoma. Who, when, how?].

Long-term survival of patients with colon carcinoma is largely determined by the timing of the diagnosis. For the identification of early colorectal carcinoma, it is of particular importance to detect and remove local precursor lesions (polyps) by means of effective screening, before they undergo malignant degeneration. The gold standard for such screening continues to be colonoscopy, followed by sigmoidoscopy, which latter, however, leaves large segments of the proximal uninspected. Additional--though less sensitive and more complicated--current screening techniques are the test for occult blood in the stools and the barium Doppler contrast examination, and, possibly in the near future, virtual colonoscopy and genetic testing for tumor DNA in the stools. Detailed screening recommendations are to be found in the guidelines issued by the German Society for Digestive and Metabolic Diseases. A prerequisite for effective prevention of colorectal carcinoma is the provision of information to, and motivation of, both the population and the individual patient, to participate in screening measures.

Adult↗

Clinical evaluation of twin screen-film chest radiography: cost effective lung and mediastinal imaging.

OBJECTIVE: A new twin screen-film cassette system optimised for conventional chest radiography was evaluated by four thoracic radiologists. MATERIALS AND METHODS: The twin screen-film cassette system produces two film images, the front film optimised for the mediastinal region of the chest, the rear for the lung region. Image degradation on either screen-film system due to internal photon scatter has been virtually eliminated due to the use of a dividing filter. Fifty patients were included in a trial that resulted in a set of chest images for each patient, taken on the same inspiration, by both the twin screen-film cassette and the conventional system. The resultant fifty sets of images were evaluated by four chest radiologists who scored 12 radiographic features of the chest and patient pathologies present, using a paired difference technique. RESULTS: The image quality of the twin screen-film cassette system was judged to be significantly superior to the conventional screen-film system in nine of the 12 radiographic features scored (P < 0.003). In the three other regions and for the patient pathologies, no significant conclusions were drawn. CONCLUSION: The new twin screen-film system showed improved visualisation of radiographic features, particularly in the mediastinal and retrocardiac lung regions. This new system shows promise in both standard and portable clinical applications.

Cost-Benefit Analysis↗

[Virtual colonoscopy].

Virtual colonoscopy is a fundamentally new imaging technique, in which volumetric CT or MRI data are processed to virtual endoscopic images of the colon. The main application is early detection of colorectal cancer. To date, no data of studies on screening for colorectal cancer are available. The results of clinical studies show comparable results for endoscopy and virtual colonoscopy for the detection of clinically relevant polyps (> or = 1 cm) and better results of virtual colonoscopy than of conventional barium studies. Whether virtual colonoscopy as a minimally invasive technique will gain a place in screening for colorectal cancer depends on several issues such as costs, effectiveness and acceptance by patients.

Colonic Polyps↗

Virtual reality and laparoscopic surgery.

The nature of laparoscopic surgery makes it likely to benefit from current and future developments in virtual reality and telepresence technology. High-definition screens, three-dimensional sensory feedback and remote dextrous manipulation will be the next major developments in laparoscopic surgery. Simulators may be used in surgical training and in the evaluation of surgical capability.

Computer Simulation↗

High-throughput screening identifies inhibitors of the SARS coronavirus main proteinase.

The causative agent of severe acute respiratory syndrome (SARS) has been identified as a novel coronavirus, SARS-CoV. The main proteinase of SARS-CoV, 3CLpro, is an attractive target for therapeutics against SARS owing to its fundamental role in viral replication. We sought to identify novel inhibitors of 3CLpro to advance the development of appropriate therapies in the treatment of SARS. 3CLpro was cloned, expressed, and purified from the Tor2 isolate. A quenched fluorescence resonance energy transfer assay was developed for 3CLpro to screen the proteinase against 50,000 drug-like small molecules on a fully automated system. The primary screen identified 572 hits; through a series of virtual and experimental filters, this number was reduced to five novel small molecules that show potent inhibitory activity (IC50 = 0.5-7 microM) toward SARS-CoV 3CLpro.

Animals↗

Computed tomography evaluation of colorectal carcinoma.

Knowledge of the extent of primary colorectal carcinoma at initial diagnosis is critical for proper management of disease. Currently, CT does not have a role in screening for colorectal carcinoma, though promising work on virtual colonoscopy is on the horizon. In patients with proven colorectal carcinoma, accurate prospective noninvasive assessment can identify those who may benefit from preoperative local radiotherapy, hepatic resection or cryoablation, or intra-arterial chemotherapy. CT should be considered complementary to the clinical assessment of colorectal carcinoma and to other modalities, such as barium enema, endorectal ultrasonography, MRI, and immunoscintigraphy. Although limited in evaluation of the primary tumor and local spread, CT has proven useful in assessing patients thought to harbor extensive local or metastatic disease. CT is generally the modality of choice for imaging the postoperative patient. The cross-sectional display of CT clearly depicts the operative bed, particularly after abdominoperineal resection. Baseline examinations should be obtained 2 to 4 months after surgery, with follow-up examinations every 6 to 9 months for 2 years, and yearly studies thereafter. CT-guided biopsies should be performed when findings suggest recurrent carcinoma.

Colon↗

Analysis of patterned injuries and injury-causing instruments with forensic 3D/CAD supported photogrammetry (FPHG): an instruction manual for the documentation process.

Forensic 3D/CAD supported photogrammetry (FPHG) is a method of recording and documenting the surface of small objects, thus enabling a three-dimensional image of these objects in virtual space. With this representation on the computer screen the course of forensically relevant events can be reconstructed. The procedure allows for examining patterned injuries of skin, soft tissue or bones for matching potentially incriminated instruments in shape, size and angle.3D recording of objects to be examined requires taking series of photographs. A computer system then calculates the position in space of certain points on the surface of the objects and subsequently produces 3D data models of the objects. Using a 3D/CAD program these data models are used to generate graphic true-to-object volume models. The objects in question can then be moved against each other arbitrarily on the screen-depending on the questions to be answered-in order to compare them and possibly establish their congruence. This article covers the state of the art in FPHG procedures in the form of a step-by-step instruction. It also illustrates the wide range of FPHG applications.

Forensic Medicine↗

Improving the results of virtual colonoscopy: what the future will bring.

Several studies show the possibility of using virtual colonoscopy in radiologic routine. To understand what its future holds, a deep insight into the techniques and pitfalls is mandatory. Currently, patient preparation and insufflation methods have to be improved because they represent the main source of pitfalls. Acquisition techniques currently provide only morphologic information, which is inadequate in the case of flat lesions. Functional information is needed but not yet available. Although the development of postprocessing techniques during the past few years has been rapid, virtual colonoscopy cannot yet be proposed as a screening technique. State-of-the-art technology, however, allows us to imagine that in the near future it will become a tool suitable for routine application.

Colonic Neoplasms↗

Virtual colonoscopy. Potential clinical applications of a new technique.

The potential role of virtual colonoscopy is not limited to colorectal cancer screening, although that is its greatest potential. Same-day VC should be offered for patients undergoing an incomplete colonoscopy. Conversely, faster, more accurate interpretation by the radiologist on the same day as a VC should lead to the consideration by the gastroenterologist of same-day colonoscopy for patients with a suspicious, significantly sized polyp.

Cohort Studies↗

"Bite-and-Switch" approach using computationally designed molecularly imprinted polymers for sensing of creatinine.

A method for the selective detection of creatinine is reported, which is based on the reaction between polymerised hemithioacetal, formed by allyl mercaptan, o-phthalic aldehyde, and primary amine leading to the formation of fluorescent isoindole complex. This method has been demonstrated previously for the detection of creatine using creatine-imprinted molecularly imprinted polymers (MIPs) Since MIPs created using traditional methods were unable to differentiate between creatine and creatinine, a new approach to the rational design of a molecularly imprinted polymer (MIP) selective for creatinine was developed using computer simulation. A virtual library of functional monomers was assigned and screened against the target molecule, creatinine, using molecular modelling software. The monomers giving the highest binding score were further tested using simulated annealing in order to mimic the complexation of the functional monomers with template in the monomer mixture. The result of this simulation gave an optimised MIP composition. The computationally designed polymer demonstrated superior selectivity in comparison to the polymer prepared using traditional approach, a detection limit of 25 microM and good stability. The "Bite-and-Switch" approach combined with molecular imprinting can be used for the design of assays and sensors, selective for amino containing substances.

Biosensing Techniques↗

Rational design of a polymer specific for microcystin-LR using a computational approach.

A computational approach for the design of a molecularly imprinted polymer (MIP) specific for Cyanobacterial toxin microcystin-LR is presented. By using molecular modeling software, a virtual library of functional monomers was designed and screened against the target toxin, employed as a template. The monomers giving the highest binding energy were selected and used in a simulated annealing (molecular dynamics) process to investigate their interaction with the template. The stoichiometric ratio observed from the simulated annealing study was used in MIP preparation for microcystin-LR. The monomers were copolymerized with a cross-linker in the presence of the template. A control (blank) polymer was prepared under the same conditions but in the absence of template. A competitive assay with microcystin-horseradish peroxidase conjugate was optimized and used to evaluate the affinity and cross-reactivity of the polymer. The performance of the artificial receptor was compared to the performance of monoclonal and polyclonal antibodies raised against the toxin. The results indicate that imprinted polymer has affinity and sensitivity comparable to those of polyclonal antibodies (the detection limit for microcystin-LR using the MIP-based assay was found to be 0.1 microg L-1), while superior chemical and thermal stabilities were obtained. Moreover, cross-reactivity to other toxin analogues was very low for the imprinted polymer, in contrast to the results achieved for antibodies. It is anticipated that the polymer designed could be used in assays, sensors, and solid-phase extraction.

Computer Simulation↗

Colon polyps and cancer.

During 1999-2000, a number of important issues related to endoscopy and colorectal polyps and cancer were investigated. Several papers consider whether flat adenomas with high malignant potential are as common in the West as in Japan. Clinical series indicate that signs of rectal bleeding are more predictive of colorectal cancer than gastrointestinal symptoms. Colonoscopy is more accurate than double-contrast barium enema for detecting polyps, and virtual colonoscopy is a promising new diagnostic and screening technique. Primary prevention dietary studies using adenoma recurrence as an end point yield negative results. Surveillance colonoscopy protects individuals in families with hereditary nonpolyposis colorectal cancer, but gastroenterologists continue to perform cancer surveillance in patients with ulcerative colitis in an inconsistent manner. Screening for colorectal neoplasia with fecal occult blood tests and flexible sigmoidoscopy is being better defined and promoted, although many now advocate direct colonoscopy screening based on increasing indirect evidence of efficacy. Better methods of treating large sessile neoplasms are being developed and evaluated, and follow-up surveillance for adenoma patients increasingly is being tailored to individual patient risk.

Colonic Neoplasms↗

Optimal digital filtering for tremor suppression.

Remote manually operated tasks such as those found in teleoperation, virtual reality, or joystick-based computer access, require the generation of an intermediate electrical signal which is transmitted to the controlled subsystem (robot arm, virtual environment, or a cursor in a computer screen). When human movements are distorted, for instance, by tremor, performance can be improved by digitally filtering the intermediate signal before it reaches the controlled device. This paper introduces a novel tremor filtering framework in which digital equalizers are optimally designed through pursuit tracking task experiments. Due to inherent properties of the man-machine system, the design of tremor suppression equalizers presents two serious problems: 1) performance criteria leading to optimizations that minimize mean-squared error are not efficient for tremor elimination and 2) movement signals show ill-conditioned autocorrelation matrices, which often result in useless or unstable solutions. To address these problems, a new performance indicator in the context of tremor is introduced, and the optimal equalizer according to this new criterion is developed. Ill-conditioning of the autocorrelation matrix is overcome using a novel method which we call pulled-optimization. Experiments performed with artificially induced vibrations and a subject with Parkinson's disease show significant improvement in performance. Additional results, along with MATLAB source code of the algorithms, and a customizable demo for PC joysticks, are available on the Internet at http:¿tremor-suppression.com.

Algorithms↗

Internal models of target motion: expected dynamics overrides measured kinematics in timing manual interceptions.

Prevailing views on how we time the interception of a moving object assume that the visual inputs are informationally sufficient to estimate the time-to-contact from the object's kinematics. Here we present evidence in favor of a different view: the brain makes the best estimate about target motion based on measured kinematics and an a priori guess about the causes of motion. According to this theory, a predictive model is used to extrapolate time-to-contact from expected dynamics (kinetics). We projected a virtual target moving vertically downward on a wide screen with different randomized laws of motion. In the first series of experiments, subjects were asked to intercept this target by punching a real ball that fell hidden behind the screen and arrived in synchrony with the visual target. Subjects systematically timed their motor responses consistent with the assumption of gravity effects on an object's mass, even when the visual target did not accelerate. With training, the gravity model was not switched off but adapted to nonaccelerating targets by shifting the time of motor activation. In the second series of experiments, there was no real ball falling behind the screen. Instead the subjects were required to intercept the visual target by clicking a mousebutton. In this case, subjects timed their responses consistent with the assumption of uniform motion in the absence of forces, even when the target actually accelerated. Overall, the results are in accord with the theory that motor responses evoked by visual kinematics are modulated by a prior of the target dynamics. The prior appears surprisingly resistant to modifications based on performance errors.

Acceleration↗

A protein phosphatase 2calpha-Ca2+ channel complex for dephosphorylation of neuronal Ca2+ channels phosphorylated by protein kinase C.

Phosphorylation and dephosphorylation are primary means for rapid regulation of a variety of neuronal functions, such as membrane excitability, neurotransmitter release, and gene expression. Voltage-gated Ca2+ channels are targets for phosphorylation by a variety of second messengers through activation of different types of protein kinases (PKs). Protein phosphatases (PPs), like PKs, are equally important in regulating Ca2+ channels in neurons. However, much less is understood about whether and how a particular type of PP contributes to regulating neuronal Ca2+ channel activities. This is primarily because of the lack of specific inhibitors/activators for different types of PPs, particularly the PP2c family. The functional roles of PP2c and its substrates in the brain remain virtually unknown. During our yeast two-hybrid screening, PP2calpha was pulled out by both N- and P/Q-type Ca2+ channel C termini. This raised the possibility that PP2calpha might be associated with voltage-gated Ca2+ channels for regulation of the Ca(2+) channel activity. Biochemical studies show that PP2calpha binds directly to neuronal Ca2+ channels forming a functional protein complex in vivo. PP2calpha, unlike PP1, PP2a and PP2b, is more effective in dephosphorylation of neuronal Ca2+ channels after their phosphorylation by PKC. In hippocampal neurons, disruption of the PP2calpha-Ca2+ channel interaction significantly enhances the response of Ca2+ channels to modulation by PKC. Thus, the PP2calpha-Ca2+ channel complex is responsible for rapid dephosphorylation of Ca2+ channels and may contribute to regulation of synaptic transmission in neurons.

Animals↗