SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
The paper reports data regarding dental caries in deciduous and permanent teeth in a sample population of 1015 pupils aged between 5 and 15, resident in the mountain community of the Chisone and Germanasca Valleys. The DMF index was significantly high, especially if one takes into account that the partial findings referring to '89 are virtually unchanged in comparison to '87.
Explore the source record for details and available documents.
BACKGROUND: In the near future advances in the molecular basis of cancer are expected to facilitate cancer diagnosis, to rationalize treatment, to facilitate screening, and to identify individuals requiring cancer prevention strategies. METHODS: The literature was reviewed concerning the genetic alterations that contribute to pancreatic cancer development. RESULTS: Virtually all pancreatic cancers have inactivation of the p16 pathway, and the majority inactivate the TGF beta/DPC4 and p53 tumor-suppressive pathways. Pancreatic cancers with mismatch repair deficiency have a characteristic histology and may have an improved prognosis. The recently discovered tumor suppressor genes, ALK-5, MKK4, and STK11 (the gene responsible for Peutz-Jeghers syndrome) are all targeted for mutation in a small proportion of sporadic pancreatic cancers. Germline mutations of the BRCA2 gene are present in 5-10% of patients with pancreatic cancer. Typically such patients do not have a family history of pancreatic cancer and are mistaken as patients with sporadic disease. Five to 10% of patients with pancreatic cancer have first-degree relatives that will develop pancreatic cancer. Some such families also have a family history of melanoma and harbor germline p16 mutations. However, the gene(s) responsible for much of the inherited predisposition to pancreatic cancer remain to be identified. CONCLUSION: Further advances in pancreatic cancer molecular genetics are needed to facilitate the development of molecular screening tests, to identify additional familial susceptibility genes, and to identify targets for rational therapeutic targeting.
The extent, severity, and irreversible nature of chronic lung disorders associated with occupation dictate careful review of any potentially mitigating measure. A genetic predisposition to lung injury is known to occur in the small percentage of individuals who are homozygous for alpha-1-antitrypsin (AAT) deficiency, a defect in the protein needed for inactivating proteolytic enzymes released after lung injury. It was found that the contribution of homozygous affected individuals to the total population at risk for chronic lung disease is too small (0.5% to 2.0%) to warrant screening. Screening could be justified if the more prevalent heterozygous AAT-deficient individuals were also at greater risk. A literature review demonstrated that up to 27.2% of persons of Spanish and 12.3% of Anglo-Saxon heritage but virtually no blacks or persons of Eastern origin are heterozygous for AAT alleles. Some heterozygous phenotypes are statistically overrepresented in hospitalized populations and among workers with impaired lung function, suggesting that they are statistically at slightly greater risk for developing lung disease than are homozygous normal individuals. These data suggest that a screen for AAT carriers would be marginally acceptable scientifically, but would pose ethical questions of discrimination and equity in use of disease-detecting resources. Review of ethical criteria for screening, particularly the availability of experimental therapies, increases the cogency and reinforces the acceptability of performing occupational tests for both homozygous and heterozygous AAT-deficient persons. Currently, programs directed at early detection of symptomatic workers coupled with reduction or elimination of offending agents are scientifically and ethically more warranted than full-scale genetic screening for AAT deficiency.
A number of nuclear hydroxy styryl ketones and related compounds were prepared and evaluated for antineoplastic and antimicrobial activities as well as for analgesic, anti-inflammatory, and antianaphylactic properties. The second-order rate constants for the reaction of several esters with hydroxide ion in aqueous dioxane (50% v/v) at 36.9 degrees were determined. The screening results showed that activity against P-388 lymphocytic leukemia was found solely with the ethers and that antimicrobial properties were obtained virtually exclusively with the phenolic derivatives. All compounds showed analgesic properties, except for four that were algesic. While little anti-inflammatory activity was found, several compounds showed some antianaphylaxis.
The experience with the submission of a nonclinical (pharmacology and toxicology) computer-assisted New Drug Application (CANDA) is reviewed. This system consisted of a stand-alone personal computer running several commercial programs in Microsoft Windows to access both text and data. WordPerfect was used as the word processor that contained all the documents and data tables (in read-only format) that were submitted in hard copy, and Andyne GQL was used as a tool to query the data in an Oracle relational database. Microsoft Excel was provided as a spreadsheet for graphics and analysis of data. Documents appeared virtually identical to those in the hard copy NDA submission. Searching the text was facilitated by the use of buttons on the screen, which allowed the NDA to be searched for a particular term. Data could be located either in WordPerfect documents, or in an Oracle database (using Andyne GQL) by querying the data. The data queries could be performed ad hoc, in which the reviewer selected all the parameters for a search, or with predefined query buttons, which retrieved data for principal treatment-related changes. This type of system also could serve as a useful model for both in-house nonclinical review and the submission of INDs and IND amendments.
Rocky Mountain Kaiser Permanente has taken aggressive steps to ensure optimal treatment of all modifiable cardiac risk factors, especially low-density lipoprotein (LDL) cholesterol, in patients with coronary artery disease. In this article, we are presenting (1) the basic rationale for our approach, (2) the critical steps translating philosophy into practice, and (3) justification for all health plans to pursue a similar course. The continuum of physician-directed disease management systems that have evolved in our region-one administered by cardiology nurses in the perihospitalization period and the other by pharmacists in the long-term, outpatient setting-is then detailed. Although the relatively short duration that our comprehensive systems have been in place precludes any assessment of their impact on cardiac death, coronary artery disease events, or coronary artery disease procedure rates, the improvements in intermediate surrogate outcomes are promising. Virtually all surveyed patients participating in our management systems have been "very" or "extremely" satisfied with their experience. The LDL-cholesterol screening rate in the approximately 2,500 participants in the programs to date has reached 97%. Of these patients, 84% have LDL cholesterol <130 mg/dL and 48% <100 mg/dL, and only 15% of those few with LDL cholesterol >130 mg/dL (2.5% overall) are currently not receiving lipid-lowering therapy. The proportions of patients on aspirin/antiplatelet and beta-blocker therapy after myocardial infarction are 97% and 92%, respectively. The lipid-screening and treatment rates, especially, represent significant improvement from our own baseline, and compare favorably with outcomes from other practice settings. In conclusion, health maintenance organizations have tremendous incentive and the unique opportunity and ability to develop systems to better manage large numbers of individuals with coronary artery disease.
Past research has indicated that many species use the time-to-collision variable but little is known about its neural underpinnings in rodents. In a set of three experiments we set out to replicate and extend the findings of Sun et al. (Sun H-J, Carey DP, Goodale MA. Exp Brain Res 1992;91:171-175) in a visually guided task in Mongolian gerbils, and then investigated the effects of lesions to different cortical areas. We trained Mongolian gerbils to run in the dark toward a target on a computer screen. In some trials the target changed in size as the animal ran toward it in such a way as to produce 'virtual targets' if the animals were using time-to-collision or contact information. In experiment 1 we confirmed that gerbils use time-to-contact information to modulate their speed of running toward a target. In experiment 2 we established that visual cortex lesions attenuate the ability of lesioned animals to use information from the visual target to guide their run, while frontal cortex lesioned animals are not as severely affected. In experiment 3 we found that small radio-frequency lesions, of either area VI or of the lateral extrastriate regions of the visual cortex also affected the use of information from the target to modulate locomotion.
Magnetic resonance imaging (MRI) has been described as the most important development in medical diagnosis since the discovery of the roentgen ray more than 100 years ago. The effectiveness of MRI has been extended to make it applicable in a wide variety of gastrointestinal disorders. The attention of gastroenterologists is currently focusing on pancreaticobiliary and bowel diseases. Magnetic resonance cholangiopancreatography (MRCP) has become a competitive alternative to diagnostic endoscopic retrograde cholangiopancreatography in a variety of hepatobiliary and pancreatic diseases. Magnetic resonance enteroscopy has the potential to become the preferable method for evaluating the entire small bowel; virtual colonoscopy, on the other hand, is far from the stage at which it could be promoted as a tool for general screening purposes in suspected colonic diseases. Its drawbacks include problems with standardization, implementation of the techniques in generalized settings, and patient acceptance.
Displaying anatomical and physiological information derived from preoperative medical images in the operating room is critical in image-guided neurosurgery. This paper presents a new approach referred to as augmented virtuality (AV) for displaying intraoperative views of the operative field over three-dimensional (3-D) multimodal preoperative images onto an external screen during surgery. A calibrated stereovision system was set up between the surgical microscope and the binocular tubes. Three-dimensional surface meshes of the operative field were then generated using stereopsis. These reconstructed 3-D surface meshes were directly displayed without any additional geometrical transform over preoperative images of the patient in the physical space. Performance evaluation was achieved using a physical skull phantom. Accuracy of the reconstruction method itself was shown to be within 1 mm (median: 0.76 mm +/- 0.27), whereas accuracy of the overall approach was shown to be within 3 mm (median: 2.29 mm +/- 0.59), including the image-to-physical space registration error. We report the results of six surgical cases where AV was used in conjunction with augmented reality. AV not only enabled vision beyond the cortical surface but also gave an overview of the surgical area. This approach facilitated understanding of the spatial relationship between the operative field and the preoperative multimodal 3-D images of the patient.
In this paper a desktop virtual reality system named Cubby is described. Cubby is based on self-induced, head-coupled movement parallax on three orthogonal screens. It is argued that this system is better suited to medical practice than Immersive VR solutions or single screen Desktop VR systems. Whilst Cubby is currently limited to visualisation it opens up possibilities of direct instrumental manipulation and as such could prove useful as a medical simulator.
INTRODUCTION: In generalized peroxisomal disorders, the clinical picture is not always obvious enough to orientate the diagnosis at an early stage of the disease. Although classic Zellweger syndrome can seldom be misdiagnosed, unless we ignore this kind of pathology altogether, the other phenotypes (neonatal adrenoleukodystrophy and infantile Refsum disease) are not always clearly delineated. Above all, the diagnosis may be difficult if we expect the patient to closely correspond to the cerebro-hepato-renal syndrome prototype. DEVELOPMENT: Thus, we must establish a series of crucial signs and symptoms that, taken together, make us suspect a peroxisomal disease and order the corresponding biochemical screening. In our experience, craniofacial dysmorphia may be misleading in the less severe phenotypes and is probably the most subjective feature. In contrast, an infant with widely open fontanels and axial hypotonia, in special if failure to thrive and/or hepatomegaly are associated, must be considered suspicious enough to make us think of a peroxisomal disorder and perform a metabolic screening. Later on in life, the neurological picture and psychomotor delay become more and more clear, and sensorineural blindness and deafness are virtually constant.
Deficiency of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme in 5-fluorouracil (5-FU) catabolism, has been linked to toxic side effects of 5-FU. The most prominent mutation of the DPD gene resulting in severe DPD deficiency is a G to A mutation in the GT 5'-splice recognition site of intron 14 (exon 14-skipping mutation). The corresponding mRNA lacks exon 14, and the enzymatic activity of the translated DPD protein is virtually absent. We developed a reverse transcription-PCR-based assay suitable for routine identification of the exon 14-skipping mutation and screened a control cohort of 851 Caucasian individuals as well as a cohort of 25 cancer patients reported by their physicians to have suffered from WHO grades 3-4 toxicity upon 5-FU chemotherapy. Within the control cohort, in total, eight heterozygotes were detected (0.94%): one heterozygote in 51 healthy donors, (1.96%); five heterozygotes in 572 hospital patients (0.87%); and two heterozygotes in 228 colorectal tumor patients (0.88%). Among the 25 patients with severe 5-FU-related toxicity, 5 (20%) were heterozygous and 1 (4%) was homozygous for the exon 14-skipping mutation. All six patients had experienced WHO grade 4 myelosuppression. Lethal outcome was seen in the homozygous and two of the heterozygous cases. We conclude that carriers of the DPD exon 14-skipping mutation are at significantly increased risk to experience life-threatening myelosuppression upon 5-FU treatment, even when the allelic status is heterozygous. These data lead us to suggest routine testing for the exon 14-skipping mutation before 5-FU treatment.
A dot immunobinding assay (DIBA) for thyrotropin (TSH) receptor antibodies is described. The method depends on the detection of antibody binding to highly purified thyroid plasma membrane attached to nitrocellulose solid support by horse-radish peroxidase - conjugated anti-human IgG. The method can detect down to 0.75 mU LATS standard and 1/1000 dilution of Graves' serum or immunoglobulin fraction. The interaction is inhibited dose-dependently by bTSH but not by insulin or human chorionic gonadotropin. The DIBA results show close correlation to those of TRAK (TBII) but not to cyclic AMP generation assay. DIBA is reproducible when tested monthly for 4 months. Sera and immunoglobulins gave virtually the same results. The method has a sensitivity of 90%, validity of 90% and specificity of 80% for both. We have, thus developed a sensitive and reliable method for screening for TSH receptor antibodies which can be performed in routine clinical laboratories.
BACKGROUND: We developed computer-based virtual patient (VP) cases to complement an interactive continuing medical education (CME) course that emphasizes skills practice using standardized patients (SP). Virtual patient simulations have the significant advantages of requiring fewer personnel and resources, being accessible at any time, and being highly standardized. Little is known about the educational effectiveness of these new resources. We conducted a randomized trial to assess the educational effectiveness of VPs and SPs in teaching clinical skills. OBJECTIVE: To determine the effectiveness of VP cases when compared with live SP cases in improving clinical skills and knowledge. DESIGN: Randomized trial. PARTICIPANTS: Fifty-five health care providers (registered nurses 45%, physicians 15%, other provider types 40%) who attended a CME program. INTERVENTIONS: Participants were randomized to receive either 4 live cases (n=32) or 2 live and 2 virtual cases (n=23). Other aspects of the course were identical for both groups. RESULTS: Participants in both groups were equivalent with respect to pre-post workshop improvement in comfort level (P=.66) and preparedness to respond (P=.61), to screen (P=.79), and to care (P=.055) for patients using the skills taught. There was no difference in subjective ratings of effectiveness of the VPs and SPs by participants who experienced both (P=.79). Improvement in diagnostic abilities were equivalent in groups who experienced cases either live or virtually. CONCLUSIONS: Improvements in performance and diagnostic ability were equivalent between the groups and participants rated VP and SP cases equally. Including well-designed VPs has a potentially powerful and efficient place in clinical skills training for practicing health care workers.
A complementation assay is described that can be used with relative safety to quantitate rapidly inhibitory effects of potential anti-HIV-1 drugs on virtually any stage of the HIV-1 life cycle by measurements of chloramphenicol acetyltransferase (CAT) activity. Of particular interest is that this system is also capable of detecting inhibition of the viral trans-activator Rev, an important potential target for drug intervention. Other applications of the system may include studies to identify domains of the envelope glycoprotein that determine infectivity and tropism or that define epitopes recognized by neutralization antibodies.
A new tool, HPLC Studio, was developed for the comparison of high-performance liquid chromatography (HPLC) chromatograms from microbial extracts. The new utility makes it possible to create a virtual chromatogram by mixing up to 20 individual chromatograms. The virtual chromatogram is the first step in establishing a ranking of the microbial fermentation conditions based on either the area or diversity of HPLC peaks. The utility was used to maximize the diversity of secondary metabolites tested from a microorganism and therefore increase the chances of finding new lead compounds in a drug discovery program.
A procedure for the qualitative assessment of inhibitory activity towards acetylcholinesterase for a given compound is described. Solutions of the compounds of interest are spotted on silica gel TLC plates in a matrix pattern. The silica gel plate is sprayed with a solution of acetylthiocholine iodide and 5,5-dithiobis(2-nitrobenzoic acid) followed by a solution of acetylcholinesterase. The enzyme reaction produces a yellow background color with inhibitor compounds exposed as white zones where color has failed to develop. The results for a test set of compounds were compared to those obtained using the standard Ellman assay procedure and found to agree for virtually all of these compounds. The conditions of silica gel plate thickness, reagent concentration, and enzyme source under which this procedure is suitable were investigated. This represents an extremely rapid method to screen large numbers of compounds to uncover new inhibitors of acetylcholinesterase and potentially other enzymes as well.