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The impact of universal screening for gestational glucose intolerance on outcome of pregnancy.

Universal screening for gestational glucose intolerance has strong support, despite the lack of scientific evidence documenting its benefit. In the early 1980s, practicing obstetricians were split concerning the clinical importance of gestational glucose intolerance, so that some practitioners tested virtually all the patients they treated while others tested none. This historical reality provided concurrent screened and unscreened populations in whom to assess the impact of screening. We studied all 1,307 singleton pregnancies cared for and delivered at the New York Hospital-Cornell University Medical Center during a five month period. Large infants (birth weight greater than or equal to 4,000 grams) were born to 10.5 per cent of the women who were not screened (533) and to 11.2 per cent of the women who were screened (774). The process of screening not only failed to decrease the rate of large infants, but also failed to improve otherwise pregnancy outcomes and was associated with more intensive surveillance during pregnancy and a significantly higher rate of primary cesarean delivery. Given the unexpected concomitants of the screening process, we conclude that recommendations for universal screening for gestational glucose intolerance should be reconsidered.

Adult↗

Manipulating and recognizing virtual objects: where the action is.

In an earlier report (Harman, Humphrey, & Goodale, 1999), we demonstrated that observers who actively rotated three-dimensional novel objects on a computer screen later showed faster visual recognition of these objects than did observers who had passively viewed exactly the same sequence of images of these virtual objects. In Experiment 1 of the present study we showed that compared to passive viewing, active exploration of three-dimensional object structure led to faster performance on a "mental rotation" task involving the studied objects. In addition, we examined how much time observers concentrated on particular views during active exploration. As we found in the previous report, they spent most of their time looking at the "side" and "front" views ("plan" views) of the objects, rather than the three-quarter or intermediate views. This strong preference for the plan views of an object led us to examine the possibility in Experiment 2 that restricting the studied views in active exploration to either the plan views or the intermediate views would result in differential learning. We found that recognition of objects was faster after active exploration limited to plan views than after active exploration of intermediate views. Taken together, these experiments demonstrate (1) that active exploration facilitates learning of the three-dimensional structure of objects, and (2) that the superior performance following active exploration may be a direct result of the opportunity to spend more time on plan views of the object.

Adolescent↗

A virtual surgical simulator for the lower limbs.

As the body of knowledge concerning human anatomy and physiology continues to grow, new techniques must emerge to convey it more efficiently to future health care professionals. Computer simulation, interaction and visualization technologies are now being used in the development of virtual training environments. This paper presents a real-time virtual surgical simulator that integrates scientific visualization tools into a surround-screen projection-based (SSPB) immersive environment. This environment focuses on procedures for the lower limbs; however, the techniques described can be applied to other portions of the body. The research consists of three phases: environment modeling, volume visualization and immersive surgical simulation. Environment modeling involved modeling an operating room with all of the relevant elements. The volume visualization phase required the application of marching cubes and decimation techniques to the Visible Human Project (VHP) dataset to generate models of the lower limbs. The simulator integrated modeling and volume visualization to facilitate the rehearsal of medical procedures and interaction with medical information. Interactive cutting, suturing and X-Ray CT placement over the virtual patient's legs were used to probe underlying structures. The simulator is intended to aid medical students in learning anatomy, physiology and radiological analysis without jeopardizing patient care.

Computer Simulation↗

Identification of differentially expressed genes in normal mucosa, adenoma and adenocarcinoma of colon by SSH.

AIM: To construct subtracted cDNA libraries and further identify differentially expressed genes that are related to the development of colorectal carcinoma(CRC). METHODS: Suppression subtractive hybridization(SSH) was done on cDNAs of normal mucosa, adenoma and adenocarcinoma tissues from the same patient. Three subtracted cDNA libraries were constructed and then hybridized with forward and backward subtracted probes for differential screening. Positive clones from each subtracted cDNA library were selected for sequencing and BLAST analysis. Finally, virtual Northern Blot confirmed such differential expression. RESULTS: By this way, there were about 3-4 X 10(2) clones identified in each subtracted cDNA library, in which about 85% positive clones were differentially screened. Sequencing and BLAST homology search revealed some clones containing sequences of known gene fragments and several possibly novel genes showing few or no sequence homologies with any known sequences in the database. CONCLUSION: All results confirmed the effectiveness and sensitivity of SSH. The differentially expressed genes during the development of CRC can be used to shed light on the pathogenesis of CRC and be useful genetic markers for early diagnosis and therapy.

Adenocarcinoma↗

Cubby: a unified interaction space for precision manipulation.

Precision manipulation in surgical simulation poses special requirements on a VR system. One such requirement is unification, i.e. that the user manipulates a virtual object where it appears. We have designed Cubby, a system of which the visualization part was presented at MMVR97 [3], for precision manipulation and unification. In an experiment Cubby was compared with a single screen head-tracked display, both in a unified and a non-unified version. The results show that subjects could manipulate virtual objects in Cubby with significantly higher accuracy and preferred it to the single screen head-tracked display. Though no significant difference in accuracy between the unified and non-unified conditions could be shown, subjects did prefer the unified over the non-unified condition within both setups.

Computer Simulation↗

Virtual reality exposure therapy for the treatment of fear of flying: a controlled investigation.

Forty-five participants who refused to fly during a screening test and who also met Diagnostic and Statistical Manual of Mental Disorders criteria for specific phobia, agoraphobia, or panic disorder with agoraphobia were randomly assigned to 5 sessions of either virtual reality exposure (VRE) or attention-placebo group treatment (GT). At posttreatment, 65% of VRE participants and 57% of GT participants flew during a test flight. Both groups showed significant improvement following treatment on standardized self-report measures of flight anxiety, with a better outcome for the VRE group on 4 of 5 of these measures. At 6-month follow-up, however, most group differences had disappeared; VRE resulted in a better outcome on only 1 of 5 standardized flight anxiety measures.

Adult↗

Discrimination of prohibited oral use of salbutamol from authorized inhaled asthma treatment.

BACKGROUND: The administration of salbutamol is permitted only by inhalation by the International Olympic Committee (IOC) for the management of asthma and exercise-induced asthma in athletes. The establishment of criteria to distinguish between the (IOC) authorized use (inhaled) and the (IOC) prohibited use (oral) of salbutamol appeared possible using simultaneous evaluation of variables based on the concentration of nonconjugated enantiomers of salbutamol excreted in urine. METHODS: Urine was collected from asthmatic and nonasthmatic swimmers who had received various preexercise doses of oral (five doses of 4 mg) or inhaled (two doses of 100 microgram) salbutamol. Urine was also obtained from subjects who had received the maximum dosage of inhaled salbutamol advisable for competing athletes to provide protection from exercise-induced asthma and treatment of asthma (1600 microgram in 24 h, 800 microgram being in the last 4 h). All samples were analyzed to determine the total amount of unchanged salbutamol excreted in urine and the ratio between the S: and R: enantiomers. RESULTS: The discriminant function D = -3.776 + 1.46 x 10(-3) ([S:(+)] + [R:(-)]) + 1.012 ([S:(+)]/[R(-)]) can be used to classify data into two groups, inhaled and oral. The confirmatory criterion suggested (cutoff at D = 1.06, 4 SD from the mean D value of the inhaled distribution) has been verified in different sets of samples showing suspicious concentrations by conventional screening procedures in doping control. An 11.8% false-negative (oral classified as inhaled) rate is assumed with the confirmatory criterion proposed, but virtually no false positives (inhaled classified as oral) are obtained (<1 in 33 000). CONCLUSIONS: The overall procedure recommended is to screen all samples and to apply the confirmation criterion proposed to samples showing free racemic salbutamol concentrations >500 microgram/L by gas chromatography-mass spectrometry or free + conjugated racemic salbutamol concentrations >1400 microgram/L by ELISA.

Administration, Inhalation↗

Comparison of ultrasound-fine needle aspiration and computed tomography in patients undergoing elective neck dissection.

BACKGROUND: Ultrasound of the neck with fine needle aspiration (US-FNA) of suspicious lymph nodes has potential advantages over other radiologic techniques as a screening method for the NO neck in head and neck cancer. METHODS: Twenty-five patients with head and neck cancer who underwent both US of the neck with FNA of any suspicious lymph nodes and neck computed tomography (CT) prior to elective neck dissection were studied. The majority of patients had squamous cell carcinoma (SCC) of the upper aerodigestive tract. Histopathologic results of the neck specimens were compared with each screening technique (palpation, US, US-FNA, CT). RESULTS: Computed tomography (87.9%) and US-FNA (84.9%) had similar overall accuracy in terms of screening the NO neck in our study and were superior to palpation (69.7%) and US alone (72.7%). Specificity was 100% for both CT and US-FNA, with a sensitivity of 60% for CT and 50% for US-FNA. Ultrasound-FNA and CT showed false-negative examinations on virtually the same cases. CONCLUSIONS: Overall, US-FNA was comparable to CT in screening the NO neck in our study. The choice of which modality to employ for imaging the clinically negative neck depends on a number of factors, including the location and clinical extent of the primary tumor as well as the experience and preference of the head and neck surgeon and radiologist.

Biopsy, Needle↗

Influence of petroleum hydrocarbon contamination on microalgae and microbial activities in a long-term contaminated soil.

Petroleum hydrocarbons are widespread environmental pollutants. Although biodegradation of petroleum hydrocarbons has been the subject of numerous investigations, information on their toxicity to microorganisms in soil is limited, with virtually no work conducted on soil algae. We carried out a screening experiment for total petroleum hydrocarbons (TPH) and their toxicity to soil algal populations, microbial biomass, and soil enzymes (dehydrogenase and urease) in a long-term TPH-polluted site with reference to an adjacent unpolluted site. Microbial biomass, soil enzyme activity, and microalgae declined in medium to high-level (5,200-21,430 mg kg(-1) soil) TPH-polluted soils, whereas low-level (<2,120 mg kg(-1) soil) pollution stimulated the algal populations and showed no effect on microbial biomass and enzymes. However, inhibition of all the tested parameters was more severe in soil considered to have medium-level pollution than in soils that were highly polluted. This result could not be explained by chemical analysis alone. Of particular interest was an observed shift in the species composition of algae in polluted soils with elimination of sensitive species in the medium to high polluted soils. Also, an algal growth inhibition test carried out using aqueous eluates prepared from polluted soils supported these results. Given the sensitivity of algae to synthetic pollutants, alteration in the algal species composition can serve as a useful bioindicator of pollution. The results of this experiment suggest that chemical analysis alone is not adequate for toxicological estimations and should be used in conjunction with bioassays. Furthermore, changes in species composition of algae proved to be more sensitive than microbial biomass and soil enzyme activity measurements.

Biomass↗

Stagewise, group sequential experimental designs for quantal responses. one-sample and two-sample comparisons.

The use of stagewise, group sequential experimental designs with dichotomous responses in toxicity or drug screening programs is discussed. Such designs represent a compromise between the standard, fixed sample size designs and fully sequential designs. Stagewise group sequential designs place specified numbers of animals on test at each stage, up to a maximum number of stages. The greatest increases in sample size efficiency occur with small numbers of stages, particularly when going from one stage to two. Two-stage designs can result in a 15 to 20 percent reduction in average sample size. Five-stage designs can result in a 30 to 40 percent reduction in average sample size, with no appreciable decrease in Type 1 error or power. Examples of the efficiencies that arose in actual screening programs are given. This paper demonstrates that the routine use of stagewise, group sequential designs in standardized screening protocols can result in substantial savings in animal use with virtually no sacrifice of statistical sensitivity.

Animals↗

A combinatorial approach to chemical modification of subtilisin Bacillus lentus.

The reaction between methanethiosulfonate reagents and cysteine mutants of subtilisin is quantitative and can be used to prepare chemically modified mutant enzymes (CMMs) with novel properties. The virtually unrestricted structural variations possible for CMMs presents a preparative and screening challenge. To address this, a rapid combinatorial method for preparing and screening the activities of CMMs has been developed.

Amino Acid Substitution↗

The apparently declining prevalence of neural tube defect in two counties in South Wales over three decades illustrating the need for continuing action and vigilance.

Neural tube defects, anencephaly and spina bifida (including encephalocele) have been the major malformation problem in South Wales. Births of affected offspring of residents of Mid and South Glamorgan between 1956 and June 1985 were ascertained from various sources. To these were added terminations following prenatal diagnosis and affected spontaneous abortions of 16 weeks gestation or more since 1973. Variable fluctuation in prevalence occurred between 1956 and 1965. Since then there has been an accelerating decline in the birth prevalence of NTD but especially of anencephaly in both counties. When abortions and terminations are taken into consideration the decline until 1984, though still present, is much slower and is virtually non-existent now. The need for continuing NTD pregnancy screening and prenatal diagnosis followed by selective abortion is stressed. It is suggested that genetic counselling health education to improve maternal nutrition preconceptional counselling and population folic acid supplementation should be extended to prevent these defects.

Abortion, Therapeutic↗

catELISA: a facile general route to catalytic antibodies.

The low abundance and activity of catalytic antibodies are major obstacles to their selection from the virtually unlimited repertoire of antibody binding sites. The requirement for new screening methodologies is further emphasized by the availability of combinatorial libraries, in which a functional polypeptide has to be selected out of millions of possibilities. We present a simple and sensitive screening approach (termed catELISA) based on immobilized substrates and immunodetection of the end product of the catalyzed reaction. The feasibility of catELISA is demonstrated here by the generation of potent ester-hydrolyzing antibodies by direct screening of hybridoma supernatants. We show that this approach is not only facile but general: it is not limited by type of reaction, substrate, or catalyst (enzymes, catalytic antibodies, chemical catalysts). catELISA opens a route to catalytic antibodies that replaces existing lengthy and arduous methods, thus allowing us to expand their number and improve their quality and to address questions that would otherwise be difficult to answer.

Animals↗

A polymerase chain reaction-based assay for the rapid detection of gene amplification in human tumors.

A differential polymerase chain reaction (PCR) protocol was established for semiquantitative, nonradioactive detection of gene amplification using a DNA sequencer. Oncogene fragments and control DNA sequences were simultaneously PCR-amplified using fluorescent-labelled primers. Analysis of the PCR products allowed quantitative assessment of gene copy numbers in this coamplification assay. Using this approach, we examined a series of 132 brain tumors for amplification of the epidermal growth factor receptor (EGFR) gene. The same set of tumors was also analyzed by Southern blotting and hybridization with a radiolabelled EGFR probe. Both methods yielded virtually identical results. This technique has a great potential for nonradioactive screening of large tumor panels of oncogene amplification.

Aneuploidy↗

Anti-V region antibodies as "almost clonotypic" reagents for the study of cutaneous T cell lymphomas and leukemias.

Despite recent advances in the understanding of normal T lymphocyte immunobiology, there has been little progress in characterizing the non-HTLV cutaneous T-cell lymphomas and leukemias (CTCL) Mycosis Fungoides and Sezary syndrome. The two major impediments to in vitro studies of these malignancies have been the contamination of CTCL cells with normal T cells and the inability to induce a vigorous proliferative response or establish long-term cultures with standard T-cell mitogens. The ideal reagent for identifying CTCL cells in a given patient would be tumor specific. Although a monoclonal antibody to the clonotypic antigen receptor on CTCL cells would approach this ideal, it is not currently feasible to generate such antibodies for each CTCL patient. As a compromise, we chose to test an "almost clonotypic" reagent by examining whether monoclonal antibodies directed at the variable (V) region of the T-cell antigen receptor could be applied to CTCL. We identified three Sezary patients, who by standard T-cell phenotype and Southern blot analysis for clonality had a virtually pure peripheral blood population of leukemic cells (PBL). We then screened the PBL of these patients with a panel of seven commercially available monoclonal anti-V region antibodies and found one patients' cells reacted greater than 99% with alpha V beta 5. The other patients' cells were non-reactive. In addition, we utilized a solid-phase system to cross-link V beta 5 on the one CTCL patients' PBL cells, and found that they proliferated vigorously in the presence of 10 units of IL-2 and IL-4. Parallel cultures have been maintained for one month by restimulation twice a week. These findings suggest that anti-V region antibodies should prove useful for investigating the immunobiology of CTCL.

Antibodies, Monoclonal↗

Location of adenomas missed by optical colonoscopy.

BACKGROUND: Previous estimates of the adenoma miss rate with optical colonoscopy (OC) are hindered by the use of OC as its own reference standard. OBJECTIVE: To evaluate the frequency and characteristics of colorectal neoplasms that are missed prospectively on OC by using virtual colonoscopy (VC) as a separate reference standard. DESIGN: Prospective, multicenter screening trial. SETTING: 3 medical centers. PARTICIPANTS: 1233 asymptomatic adults who underwent same-day VC and OC. MEASUREMENTS: Colorectal neoplasms (adenomatous polyps) missed at OC before VC results were unblinded. RESULTS: Fourteen (93.3%) of 15 nonrectal neoplasms were located on a fold; 10 (71.4%) of these were located on the backside of a fold. Five (83.3%) of 6 rectal lesions were located within 10 cm of the anal verge. LIMITATIONS: Estimation of the OC miss rate depended on polyp detection on both VC and second-look OC and therefore underestimates the true OC miss rate, particularly for smaller polyps. CONCLUSIONS: Most clinically significant adenomas missed prospectively on OC are located behind a fold or near the anal verge. The 12% OC miss rate for large adenomas (>or=10 mm) when state-of-the-art 3-dimensional VC is used as a separate reference standard is increased from the previous 0% to 6% estimates derived by using OC as its own reference standard.

Adenoma↗

[Chalcones (1,3-diarylpropen-1-ones) and their analogs as potential therapeutic agents in cardiovascular system diseases].

At the beginning of a new millennium, several important questions have come to the fore connected with the utilization of natural resources for the investigation of new medicaments (necessity of cooperation of both highly developed and developing countries in the protection of natural resources, necessity to justly evaluate and reward the contributions of the individual cultures in the case that a knowledge of traditional medicine was employed in the development of a new medicament, necessity to achieve the maximal chemical variety of real and virtual libraries of substances from which potential drugs are selected for screening tests). The research of chalcones and its analogues which are relatively easily available not only by isolation from natural material, but also by the methods of classical and combinatorial synthesis should not be substantially affected by the above-described changes. The present communication links up with previous papers (Opletalová, V., Sedivý, D.: Ces. slov. Farm. 48, 252 (1999); Opletalová, V.: Ces. slov. Farm. 49, 278 (2000); Opletalová, V. et al.: Folia Pharm. Univ. Carol. 25, 21 (2000)) and is devoted to the stabilizing action of chalcones on the vascular wall, vasodilating and anti-aggregating effects, and a favourable effect of their antioxidative activity on the functions of the cardiovascular system. The introduction also briefly discusses the nomenclature of this group of compounds.

Animals↗

Current colorectal cancer screening strategies: overview and obstacles to implementation.

Colorectal cancer is the second leading cause of cancer death but is largely preventable. Current strategies to prevent colorectal cancer vary considerably with regard to effectiveness, up-front costs, risks, and invasiveness. Current levels of participation in colorectal cancer screening in the U.S. population are low. Both physician and patient attitudes contribute to low levels of screening uptake. New colorectal cancer tests are one mechanism to improve adherence. Virtual colonoscopy may have an important impact if techniques to perform it without bowel preparation can be developed. Stool-based DNA testing is likely to be the most effective entirely noninvasive strategy and will be easier for patients to perform than fecal occult blood testing. The potential for improvements in the technology are substantial, and data from second-generation assays have already been reported. The cost-effectiveness of new strategies needs further evaluation.

Barium Sulfate↗