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At least 775 records · Page 43Linked to original sources
PubMed2000

Cervical cancer screening in developing countries.

In developing countries, cervical cancer remains a clinical problem of public health proportions. Eighty percent of the approximately 400,000 new cases of cervical cancer each year occur in such settings. Primarily as a result of the introduction and success of screening programs, cervical cancer rates in developed countries have dropped remarkably. However, in most developing countries, screening programs are virtually nonexistent. Reasons for this relate primarily to lack of public awareness and the fact that screening via cytology is an untenable proposition for mass screening in such low-resource settings. Matching the resources available to provide cervical cancer screening in such settings requires alternative means of providing testing and treatment. Recent evidence indicates that, depending on local conditions and locally-made decisions, visual inspection of the cervix with acetic acid wash, coupled with a benign form of therapy, such as cryotherapy, could hold promise as a means of testing and treatment. By adapting resource-appropriate technologies and building local consensus regarding clinically driven public health approaches that are safe and feasible, the challenge of reducing the mortality from cervical cancer in developing countries can yet be met.

Journal Article↗
PubMed2000

Examination of the chin or lower abdomen only for the prediction of hirsutism.

OBJECTIVE: To test the hypothesis that scoring terminal hair growth on only the chin or abdomen can serve as a reliable predictor for hirsutism. DESIGN: A prospective observational study. PATIENT(S): Six hundred and ninety-five consecutive hyperandrogenic women seen between June 1987 and December 1997. MAIN OUTCOME MEASURE(S): All hirsutism exams were performed by one examiner. Hirsutism was scored using a modification of the Ferriman-Gallwey (F-G) method. An F-G score of > or = 8 defined hirsutism. RESULT(S): Of the 695 women examined 352 (50.1%) had hirsutism scores of 8. Thirty percent (79 of 344) of women who had an F-G score of <8 had previously underwent electrology. If either the chin or lower abdomen hair growth score was > or = 2, the sensitivity was 100% for the prediction of hirsutism, although the specificity was 27%. The positive predictive value (PPV) for hirsutism using a hair score of > or = 2 at either of these sites was 58%. CONCLUSION(S): A hair growth score of > or = 2 on the chin or lower abdomen only was found to be a highly sensitive predictor for hirsutism. However, because of its very low PPV, this screening method is virtually useless in populations where the hirsutism frequency is expected to be low, about 5%. However, this screening method for the detection of hirsutism would be useful for the study of high-risk populations with an expected hirsutism prevalence of >20% (e.g., family studies).

Abdomen↗
PubMed2003

NMR-based screening methods for lead discovery.

Diversity and robustness of NMR based screening methods make these techniques highly attractive as tools for drug discovery. Although not all screening techniques discussed here may be applicable to any given target, there is however a good chance that at least one of the described methods will prove productive in finding several medium affinity ligands. A comparison of each of the methods is given in Table 1. For drug targets of molecular weight < 30 kDa SAR by NMR appears to be the method of choice since it yields detailed information about the location of the binding site. It remains to be seen whether 15N-1H-TROSY based screening techniques will prove useful for larger protein targets, especially considering the added effort needed for spectral assignment and the increased complexity due to spectral overlap. Nevertheless, with the application of new cryo-cooled NMR probes, 15N-1H-HSQC based screening can now be considered a high throughput method. Ligand-based NMR screening methods can be used for protein targets of virtually any size, but are restricted in the ligand's binding affinity range. Because sufficient ligand-protein dissociation rates are needed, only binding of ligands with low (milimolar) to intermediate (micromolar) affinities is detectable. It is expected that cryo-cooled NMR probe technology will also advance ligand detected NMR screening to the high throughput level. Certainly protein and ligand concentrations can be lowered drastically and experiment times can be shortened with increased sensitivity. However, spectral overlap will be of major concern when mixtures of up to 100 compounds are to be screened. For such applications only techniques for which the signals of bound ligands survive will be useful, and sophisticated software will be needed to deconvolute the spectra of multiple bound ligands. Although only ligands with medium to low affinities can be found, ligand based NMR screening has been used as an effective prescreening tool for assay based high throughput screening. Identifying a large ensemble of medium affinity ligands may not only aid in building a binding site pharmacophore model (see Chapter 11), but also may yield crucial information for overcoming tissue availability, toxicity, or even intellectual property related problems. Although NMR based screening is only one of the more recent additions to the bag of tools used in drug discovery [1, 2], its simplicity and wide range of application (including protein-protein and protein-nucleic acid interactions) has attracted much attention. Advances in NMR instrumentation and methodology have already paved the road for NMR based screening to become a high throughput technique. In addition to this, NMR is exceptional in the amount of detailed structural [table: see text] information it can provide. Not only can NMR readily reveal the binding site (15N-1H-HSQC screening) or the conformation of the bound ligand (transfer NOE), but it can also supply information that enables precise docking of the ligand to the protein's binding pocket (isotope-filtered NOESY). NMR data can therefore provide a natural connection between experimental HTS and combinatorial chemistry techniques with computational methods such as 3D-database searching (see Chapter 10), virtual screening (docking) and structure-based ligand design (see also Chapter 8).

Animals↗
PubMed2004

[Efficiency of hepatitis C virus screening before and after blood transfusion].

UNLABELLED: Efficiency of a viral hepatitis C screening strategy before and after blood transfusion has to be evaluated. METHODS: Four screening strategies were virtually applied to the population of transfused patients at Rouen University Hospital during 1996 and then compared : the first without any systematic HCV screening test; the second with systematic testing both before and 3 months after transfusion; the third with systematic testing both before and 6 months after transfusion ; the last defined as systematic testing before transfusion only. The efficacy (i.e. number of positive tests), the efficiency (i.e. average cost per positive test) and the marginal costs of moving from a strategy to another one were assessed using decision analysis. RESULTS: The efficacy of systematic screening test before transfusion only (361 per positive test), systematic testing both before and three months after (523 per positive test) or six months after (488 per positive test) transfusion was similar, but the efficacy of the strategy without any systematic screening test (385 per positive test) was lower. The systematization of screening test both before, and three months, or 6 months after transfusion lead to a marginal cost of 619 , and 559 per positive test respectively. The systematization of testing before transfusion only lead to a marginal cost of 343 per positive test. Adding systematic testing after transfusion lead to a marginal cost of 5824 per positive test. CONCLUSION: Systematic screening tests before transfusion only can be considered as the most efficient strategy.

Blood Transfusion↗
PubMed2006

Provision of contraceptive and related services by publicly funded family planning clinics, 2003.

CONTEXT: In addition to contraceptive services, publicly funded family planning clinics provide low-income women with a range of reproductive diagnostic, treatment and educational services. Nationally representative information about the scope of services available from clinics is needed to formulate policy and programmatic recommendations. METHODS: In 2003, more than 1,000 U.S. clinics responded to an eight-page survey on service availability and clinic policies. Differences in the proportions of clinics reporting each service or policy were examined by clinic type and receipt of Title X funding. RESULTS: Nearly all clinics offer pills, injectables and condoms; 75% offer the patch; and 80% offer emergency contraception. Most clinics (73%) typically use a conventional Pap smear for initial cervical cancer screenings; 27% use liquid-based Pap tests. For follow-up, 68% of clinics use liquid-based or other advanced testing. Virtually all clinics screen at least some clients for chlamydia; Planned Parenthood and Title X-funded clinics, more than others, tend to focus screening efforts on sexually active women aged 25 and younger. Single-dose treatments are provided by 58% of clinics. Nine in 10 clinics offer HIV testing on-site, most of them to any client who requests it. Services targeted to specific populations include counseling about abstinence for minors (91%); non-reproductive health services for men (36%); and availability of staff such as translators (81%) and bilingual administrative (59%) or clinical personnel (57%) for non-English-speaking clients. CONCLUSIONS: More public funding is imperative for clinics to keep up with the demands of new technologies and a diverse client base.

Adolescent↗
PubMed1996

Comparison of the abilities of serologic tests to detect pseudorabies-infected pigs during the latent phase of infection.

OBJECTIVE: To compare the sensitivities of all available serologic tests in detecting pseudorabies virus (PRV) antibodies in pigs during long-term latent pseudorabies. DESIGN: Pigs experimentally infected with a virulent strain of PRV were maintained for 2 to 27 months after inoculation. At the time of necropsy of each pig, blood was collected for serologic evaluation, and tissues were obtained for polymerase chain reaction (PCR) verification of latency. ANIMALS: 65 crossbred pigs each weighing approximately 18 kg at the start of the study. PROCEDURE: Serum samples from each pig were analyzed by serum neutralization, latex agglutination, screening ELISA, particle concentration fluorescence immunoassay, automated latex agglutination, and differential ELISA for glycoproteins I, III, and X. DNA was extracted from the trigeminal ganglia and tonsils of each pig and was analyzed by PCR for PRV genomic sequences. RESULTS: PCR analysis of trigeminal ganglia and tonsils indicated that all pigs were latently infected with PRV at the time of necropsy, and serologic testing verified that all pigs had PRV-specific antibodies, regardless of duration of infection. The screening tests were virtually equivalent in sensitivity for detection of PRV antibodies. Of the differential serologic tests, the glycoprotein-I and -III marker systems, which performed with similar sensitivity as screening tests, were superior to the glycoprotein-X marker system in detecting PRV antibodies in latently infected pigs. CONCLUSION: Serologic testing consistently detects pigs in the latent phase of PRV infection, provided that the test detects the antibody response to the whole virus or to a reliable PRV-marker glycoprotein.

Animals↗
PubMed2007

Automated multiple ligand screening by frontal affinity chromatography-mass spectrometry (FAC-MS).

High-throughput screening (HTS) efforts to discover "hits" typically rely on the large-scale parallel screening of individual compounds with attempts to screen mixtures of compounds typically and, unfortunately, giving rise to false positives and false negatives due to the nature of the HTS readout (% inhibition/activation above a defined threshold) that makes deconvolution virtually intractable. Bioaffinity screening methods have emerged as an alternative or orthogonal method to classic HTS. One of these methods, frontal affinity chromatography coupled to mass spectrometry detection (FAC-MS), although still a relatively new technique, is turning out to be a viable screening tool. However, to push FAC-MS more to the forefront as a moderate primary HTS system (or a secondary screening assay), automation needs to be addressed. An automated FAC-MS system is described using 2 columns containing immobilized hERbeta, whereby while 1 column is being regenerated, the other is being used. The authors are extrapolating that in a continuous 24-h operation, the number of ligands screened could potentially approach 10,000. In addition, preliminary structure-activity relationship binding information (typically not seen in early primary HTS) can be obtained by observing the rank order of the library members in the various mixtures.

Amino Acid Sequence↗
PubMed2006

Financing state newborn screening programs: sources and uses of funds.

BACKGROUND: Financing for newborn screening is different from virtually all other public health programs. All except 5 screening programs collect fees as the primary source of program funding. A fee-based approach to financing newborn screening has been adopted by most states, to ensure consistent funding for this critical public health activity. METHODS: Two types of data are reported here, ie, primary data from a survey of 37 state public health agencies and findings from exploratory case studies from 7 states. RESULTS: Most of the programs that participated in this survey (73%) reported that their newborn screening funding increased between 2002 and 2005, typically through increased fees and to a lesser extent through Medicaid, Title V Maternal and Child Health Services Block Grant, and state general revenue funding. All of the responding states that collect fees (n = 31) use such funds to support laboratory expenses, and most (70%) finance short-term follow-up services and program management. Nearly one half (47%) finance longer-term follow-up services, case management, or family support beyond diagnosis. Other states (43%) finance genetic or nutritional counseling and formula foods or treatment. CONCLUSIONS: Regardless of the source of funds, the available evidence indicates that states are committed to maintaining their programs and securing the necessary financing for the initial screening through diagnosis. Use of federal funding is currently limited; however, pressure to provide dedicated federal funding would likely increase if national recommendations for a uniform newborn screening panel were issued.

Data Collection↗
PubMed2005

Discovery of ligands by a combination of computational and NMR-based screening: RNA as an example target.

NMR for screening of knowledge-based focused libraries of compounds provides an efficient, cost-effective method to develop promising drug leads that target functionally important RNA structures. A knowledge-based focused library may be constructed from virtual (i.e., computational) screening of commercial or proprietary databases of available compounds for binding to the three-dimensional structure of a selected RNA target. Alternatively, the library may be constructed from compounds with properties deemed desirable, e.g., molecular moiety commonly found in drugs or known to bind RNA. The library ideally should be composed of small water-soluble, nonpeptide, nonnucleotide organic compounds. Various simple, robust NMR experiments are described that enable experimental screening of such a library for binding to a selected RNA structure. Some of the NMR experiments enable rapid mapping of the interaction site on the RNA to verify that the targeted structure is hit rather than the double helical region or a commonly occurring tetraloop. Other experiments enable elucidation of the ligand's binding moiety. Of course, any compounds thus identified should represent promising scaffolds suitable for easy chemical modification to enhance their pharmaceutical properties for subsequent drug development.

Computational Biology↗
PubMed2002

Scalable methods for the construction and analysis of virtual combinatorial libraries.

One can distinguish between two kinds of virtual combinatorial libraries: viable and accessible . Viable libraries are relatively small in size, are assembled from readily available reagents that have been filtered by the medicinal chemist, and often have a physical counterpart. Conversely, accessible libraries can encompass millions or billions of structures, typically include all possible reagents that are in principle compatible with a particular reaction scheme, and they can never be physically synthesized in their entirety. Although the analysis of viable virtual libraries is relatively straightforward, the handling of large accessible libraries requires methods that scale well with respect to library size. In this work, we present novel, efficient and scalable techniques for the construction, analysis, and in silico screening of massive virtual combinatorial libraries.

Combinatorial Chemistry Techniques↗
PubMed1995

A virtual reality environment for enhanced oral implantology.

The quality of clinical decision making is limited by the performance of human cognitive processing of complex visual information. In the field of oral implantology, treatment planning is still based on the holistic interpretation and mental reconstruction of cross sectional 2d-image data. This surpasses widely human cognitive competence and hampers treatment planning in three dimensions that are essential in implantology. To overcome these problems, a virtual reality environment for enhanced treatment planning in oral implantology is presented, which provides a fully three-dimensional perception of an individual clinical situation. It enables the clinician to perceive and handle the objects of her work in a virtual world as needed for the task of diagnosis and treatment. Human visual decoding effort is thus reduced, and estimating the real position and orientation of implants during planning is enabled in any direction. Immersive three-dimensional perception is achieved by hybrid stereoscopic rendering techniques combined with large screen projections. The virtual world in which treatment planning takes place allows the clinician to move and interact with the individual anatomy simultaneously with three degrees of freedom. A set of virtual tools enables the clinician to perform a virtual treatment "in advance." The design and placement of implants, as it is interactively controlled by the clinician, is simulated in real-time. Thus the results of actions become immediately visible and provide visible feedback for interactive adjustment. In addition, the presented virtual reality environment for oral implant treatment planning includes algorithms for detection of inappropriate treatment in the concerned bone regions, according to the current design of the implant. These algorithms take both the individual properties of a patient's bone and the type of implants used into account.

Computer Simulation↗
PubMed2005

Combinatorial design of nonsymmetrical cyclic urea inhibitors of aspartic protease of HIV-1.

The aspartic protease (PR) of the human immunodeficiency virus type 1 (HIV-1) is an important target for the design of specific antiviral agents dedicated to treatment of HIV-1 infection. We have employed computer-assisted combinatorial chemistry methods to design a small focused virtual library of nonsymmetrically substituted cyclic urea inhibitors of the PR. Nonsymmetrical compounds with decreased peptidic character were namely found to inhibit the PR with comparable inhibition potencies as their C2-pseudosymmetric counterparts and to possess superior pharmacokinetic properties. To generate the virtual library of fully nonsymmetrical cyclic urea analogs, diverse reagents were selected from databases of available chemicals with characteristics similar to those of the building blocks of known potent PR inhibitors. The X-ray structure of the protease-inhibitor complex PR-XV-638 was used as the receptor model in the structure-based focusing and in silico screening of the virtual library. A target-specific LUDI-type scoring function, parameterized for a QSAR training set of known cyclic urea inhibitors and validated on a set of compounds not included into the training set, was used to predict the inhibition constants (Ki) of the generated analogs toward the HIV-1 PR. The fragments most frequently occurring in the analogs with the highest predicted inhibition potencies (Ki*<10 pM) were then selected to constitute a highly focused library subset containing novel nonsymmetrical cyclic ureas with predicted Ki*s 1 order of magnitude lower than the most potent known cyclic urea inhibitors. ADME properties calculated for the most promising analogs suggested that the cyclic ureas are endowed with a wide range of favorable pharmacokinetic properties, which may favor the discovery of a potent orally administrable antiviral drug.

Combinatorial Chemistry Techniques↗
PubMed2005

Here be dragons: docking and screening in an uncharted region of chemical space.

To compare virtual and high-throughput screening in an unbiased way, 50,000 compounds were docked into the 3-dimensional structure of dihydrofolate reductase prospectively, and the results were compared to a subsequent experimental screening of the same library. Undertaking these calculations demanded careful database curation and control calculations with annotated inhibitors. These ultimately led to a ranked list of more likely and less likely inhibitors and to the prediction that relatively few inhibitors would be found in the empirical screen. The latter prediction turned out to be correct, with arguably no validated inhibitors found experimentally. Subsequent retesting of high-scoring docked molecules may have found 2 true inhibitors, although this remains uncertain due to experimental ambiguities. The implications of this study for screening campaigns are considered.

Computational Biology↗
PubMed2004

TOMOCOMD-CARDD, a novel approach for computer-aided 'rational' drug design: I. Theoretical and experimental assessment of a promising method for computational screening and in silico design of new anthelmintic compounds.

In this work, the TOMOCOMD-CARDD approach has been applied to estimate the anthelmintic activity. Total and local (both atom and atom-type) quadratic indices and linear discriminant analysis were used to obtain a quantitative model that discriminates between anthelmintic and non-anthelmintic drug-like compounds. The obtained model correctly classified 90.37% of compounds in the training set. External validation processes to assess the robustness and predictive power of the obtained model were carried out. The QSAR model correctly classified 88.18% of compounds in this external prediction set. A second model was performed to outline some conclusions about the possible modes of action of anthelmintic drugs. This model permits the correct classification of 94.52% of compounds in the training set, and 80.00% of good global classification in the external prediction set. After that, the developed model was used in virtual in silico screening and several compounds from the Merck Index, Negwer's handbook and Goodman and Gilman were identified by models as anthelmintic. Finally, the experimental assay of one organic chemical (G-1) by an in vivo test coincides fairly well (100%) with model predictions. These results suggest that the proposed method will be a good tool for studying the biological properties of drug candidates during the early state of the drug-development process.

Animals↗
PubMed2005

The IARC commitment to cancer prevention: the example of papillomavirus and cervical cancer.

Every year approximately half a million women worldwide develop cervical cancer (CC) of whom 80% live in poor countries where population-based screening programmes are virtually non-existent. The role of sexually transmitted agents in the aetiology of cervical cancer has been suspected for more than a century, but knowledge in this field has rapidly expanded only in the last 20 years, after major improvements were made in detection methods for human papillomavirus (HPV). A dozen types of HPV have been identified in 99% of biopsy specimens from CC worldwide and the relative risk estimates for HPV in case-control studies of CC are in the 50 to 100 range. A meta-analysis done at the International Agency for Research on Cancer (IARC) included a total of 10,058 CC cases from 85 published studies. The most common HPV types identified in CC were, in order of decreasing prevalence, HPV 16, 18, 45, 31, 33, 58, 52, 35, 59, 56, 6, 51, 68, 39, 82, 73, 66 and 70. Over two-thirds of CC cases were associated with an infection of either HPV 16 (51.0%) or HPV 18 (16.2%). Despite the overwhelming importance of HPV, other factors contribute to the rare occurrence of CC after HPV infection. Nine case-control studies from the IARC have confirmed the adverse effect of long-term use of oral contraceptives, high parity, smoking and sexually transmitted infections (i.e. Chlamydia trachomatis and herpes simplex virus-2) after adjustment for, or stratification by, HPV infection. Ten surveys of HPV infection in population-based samples of approximately 15,000 women in four continents have shown that: (1) the prevalence of HPV infection varies greatly (between 2% and nearly 30%); and (2) the age distribution also varies widely, pointing to cohort effects. There is no effective medical treatment for HPV, but a prophylactic vaccine, based on late (L) 1 HPV 16 proteins, has been shown to be safe, highly immunogenic and efficacious in preventing persistent HPV infections. A multivalent vaccine against the most common oncogenic HPV types may thus ultimately represent the most effective way to prevent CC worldwide either alone, or in combination with screening. It may, however, take several years before this approach becomes a reality. Thus, early detection of CC precursor lesions by screening, and their treatment, will remain the most important measures for the control of CC for the foreseeable future.

Female↗
PubMed2001

Sickle cell.

The initiation of newborn screening and its virtually universal implementation will eventually yield a population in which sickle cell disease has been identified and comprehensive care is provided for children. The situation with SCT is different; there will continue to be the identification of parents who have the potential for having a child with a sickle cell disease but because they will not be tested or counseled, there will continue to be a population of children with a sickle cell disease whose parents have not been enabled to make informed decisions that they believe are in their best interest relative to family planning. Also, we will continue to have a population of pregnant women with a fetus with sickle cell disease who will not be given an opportunity to decide whether they wish to continue or terminate the pregnancy. They all will give birth to a child with a lifetime of chronic illness with its associated psychological, social, and financial burdens for the individual and his or her parents. The failure to implement prenatal diagnosis is an abridgment of two fundamental rights: the right to know and the right to decide. In this case it is the right to know about the potential health status of their children if that is possible, and the right to decide about the actual health care status of their children if options are available.

Anemia, Sickle Cell↗