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PubMed2004

Serial analysis of gene expression in neurofibromatosis type 2-associated vestibular schwannoma.

HYPOTHESIS: The genesis, morphology, and growth characteristics of vestibular schwannomas are determined by genetic alterations which vary gene transcript expression and this transcript expression can be qualitatively and quantitatively evaluated using the SAGE technique. By use of such technique, gene products with tumorigenic potential may be identified, providing insight and targets for future study. BACKGROUND: Serial analysis of gene expression (SAGE) is a powerful new technique that allows detailed qualitative and quantitative evaluation of cellular gene transcript expression. Tissue in limited quantity (5 x 10 to 2 x 10 cells) may be analyzed by a modified version of SAGE called microSAGE. Application of SAGE or microSAGE to study vestibular schwannoma gene expression has not been previously reported. METHODS: Fresh, vestibular schwannoma specimen from an individual with the diagnosis of neurofibromatosis type 2 was attained intraoperatively and maintained in a sealed container at -80degreesC until the time of analysis. The tissue was processed according to the microSAGE protocol, using 180 mg of vestibular schwannoma as starting material. RESULTS: The protocol resulted in the generation and sequencing of a tag library involving 458 tags representing 277 different gene products, including many transcripts known to be expressed in vestibular schwannomas. Several gene products with tumorigenic potential were identified. CONCLUSIONS: These data demonstrate that microSAGE is a useful technique to study vestibular schwannoma gene expression. Future studies will include building more comprehensive libraries and comparing libraries from various vestibular schwannoma phenotypes to identify useful diagnostic or prognostic markers, and targets for therapeutic intervention.

Adult↗
PubMed2005

Antibiotic prophylaxis for transurethral prostatic resection in men with preoperative urine containing less than 100,000 bacteria per ml: a systematic review.

PURPOSE: We determined whether antibiotic prophylaxis can reduce the risk of postoperative infective complications in men undergoing transurethral resection of the prostate (TURP) who have preoperative urine with less than 100,000 bacteria per ml. MATERIALS AND METHODS: MEDLINE, EMBASE (Elsevier B.V., Amsterdam, The Netherlands) and the Cochrane Library were searched for randomized and quasi-randomized controlled trials that compared the effects of antibiotic prophylaxis with placebo or active controls for men undergoing TURP with preoperative sterile urine. Two reviewers independently extracted patient characteristic and outcomes data based on a prospectively developed protocol. RESULTS: A total of 28 trials, 10 placebo controlled and 18 no treatment controlled, involving 4,694 patients, met the inclusion criteria. The mean age of the subjects was 69 years and the majority underwent TURP for prostatic hyperplasia (85%). Antibiotic prophylaxis was significantly more effective than placebo in reducing postoperative TURP complications. The risk differences for post-TURP bacteriuria, high degree fever, bacteremia and use of additional antibiotic treatment were -0.17 (95% CI 0.20, -0.15), -0.11 (-0.15, -0.06), -0.02 (-0.04, 0.00) and -0.20 (-0.28, -0.11), respectively. The results were observed consistently across all classes of antibiotics assessed. There was no difference in the duration of postoperative catheterization or hospitalization. Adverse events were rare, generally mild, and included allergic reactions, pyrexia and abdominal complaints. CONCLUSIONS: Prophylactic antibiotics decrease the incidence of post-TURP bacteriuria, high fever, bacteremia and additional antibiotic treatment. Additional research should evaluate the optimal antibiotic regimen, and whether the cost and possibility of the development of resistant strains of organisms justify the routine use of prophylactic antibiotics.

Aged↗
PubMed1993

Characterization of a tryptase mRNA expressed in the human basophil cell line KU812.

The expression of a tryptic serine protease was detected in the cell line KU812 by Northern blot analysis with an oligonucleotide probe directed against a conserved region present in all of the five presently cloned human mast cell tryptases. PCR primers designed for the amplification of a nearly full-length copy of tryptase mRNAs were used to study the identity of the KU812 tryptase. Ten clones were characterized and all were found to be identical to one of the tryptases previously cloned from a human skin cDNA library. This tryptase has been thought to originate from mast cells of the skin. Two possible explanations may account for the observed identity between the presumed mast cell tryptase and the KU812 tryptase. Firstly, it is possible that the KU812 tryptase is a basophil-specific tryptase which has previously been cloned from a human skin cDNA library containing low levels of cDNA copies derived from basophils in the starting material. Secondly, the KU812 cell line, and possibly normal basophils, express a tryptase which is identical to one of the tryptases expressed in normal skin mast cells. We cannot at present rule out any of the two possibilities, but we favour the second explanation as being the most likely.

Base Sequence↗
PubMed2006

Developmental dysplasia of the hip: quality of reporting of diagnostic accuracy for US.

PURPOSE: To systematically review the quality of diagnostic accuracy reporting in studies on the use of ultrasonography (US) for the diagnosis of developmental dysplasia of the hip (DDH). MATERIALS AND METHODS: A systematic review of the MEDLINE, EMBASE, DARE, and Cochrane Library databases was performed by using a validated search strategy. Two independent reviewers evaluated articles by using the Standards for Reporting of Diagnostic Accuracy (STARD) and Quality Assessment of Studies of Diagnostic Accuracy included in Systematic Reviews (QUADAS) statements. Items were reported individually for STARD and QUADAS because these instruments do not incorporate a summary score. A simple kappa statistic with 95% confidence intervals was used to measure the level of agreement between the two reviewers. RESULTS: Ten studies were included. In three studies, reliability was investigated, and in seven studies elements of both validity and reliability were investigated. In no study did the authors adequately report more than 40% of the STARD items. The quality of methods that were used in the studies was poor. Only one (14%) of seven studies provided information on more than 50% of the QUADAS items. All studies included a good description of image acquisition, but data analysis was imperfect and lacked estimates of diagnostic accuracy and precision. Authors tended to overinterpret their results. CONCLUSION: Overall, there was imperfect reporting of diagnostic accuracy in studies on the use of US for diagnosis of DDH.

Hip Dislocation, Congenital↗
PubMed2006

Biodiversity as a source of anticancer drugs.

Natural Products have been the most significant source of drugs and drug leads in history. Their dominant role in cancer chemotherapeutics is clear with about 74% of anticancer compounds being either natural products, or natural product-derived. The biodiversity of the world provides a resource of unlimited structural diversity for bioprospecting by international drug discovery programs such as the ICBGs and NCDDGs, the latter focusing exclusively on anticancer compounds. However, many sources of natural products remain largely untapped. Technology is gradually overcoming the traditional difficulties encountered in natural products research by improving access to biodiverse resources, and ensuring the compatibility of samples with high throughput procedures. However, the acquisition of predictive biodiversity remains challenging. Plant and organism species may be selected on the basis of potentially useful phytochemical composition by consulting ethnopharmacological, chemosystematic, and ecological information. On the conservation/political front, the Convention on Biological Diversity (CBD) is allaying the anxiety surrounding the notion of biopiracy, which has defeated many attempts to discover and develop new natural products for human benefit. As it becomes increasingly evident and important, the CBD fosters cooperation and adaptation to new regulations and collaborative research agreements with source countries. Even as the past inadequacies of combinatorial chemistry are being analyzed, the intrinsic value of natural products as a source of drug leads is being increasingly appreciated. Their rich structural and stereochemical characteristics make them valuable as templates for exploring novel molecular diversity with the aim of synthesizing lead generation libraries with greater biological relevance. This will ensure an ample supply of starting materials for screening against the multitude of potentially "druggable" targets uncovered by genomics technologies. Far from being mutually exclusive, biodiversity and genomics should be the driving force of drug discovery in the 21st century.

Animals↗
PubMed2001

Practical recommendations for the use of acupuncture in the treatment of temporomandibular disorders based on the outcome of published controlled studies.

OBJECTIVE: The objective is to analyse the treatment procedures used in the individual studies to identify any similarities of therapeutic approaches and subsequently present recommendations for a standard acupuncture procedure for the treatment of temporomandibular disorders (TMD). MATERIALS: Literature searches performed by the Royal Society of Medicine and the University Library, Copenhagen were able to identify 74 publications regarding the use of acupuncture in dentistry. Among them 14 papers concerned the use of acupuncture in the treatment of TMD. To ensure reasonable methodological soundness of the involved studies, only randomised and blinded studies were included, which reduced the number of papers to six. Among these six papers three concerns the same study and were counted as one. One paper was a follow-up of a previous study and for this purpose counted as one. METHODS: All publications were analysed for the following information: acupuncture points used, type of stimulation, number of treatments, duration of the individual treatment and the interval between the individual treatments. MAIN OUTCOME: Acupuncture has in three out of three randomised controlled trials (RCT) proved effective for the treatment of TMD. The following local acupuncture points are recommended for the treatment of TMD: ST-6, ST-7, SI-18, GV-20, GB-20, BL-10. As a distant point LI-4 is recommended. After inserting the needles they should be manipulated manually to achieve the De-qui sensation and left in situ for 30 min. Treatment should be given weekly and a total number of six treatments is recommended.

Acupuncture Points↗
PubMed2001

[Diversity and selectivity in biomolecules].

Nature provides molecular constructions in inexhaustible richness. She combines small building blocksacks, and from the great variety of the possible structures, the really existing molecules are selected by kinetic (actually enzymic) and thermodynamic control. The operation of this fundamental principle is demonstrated by means of the graph analysis, in the large community of the monoterpenoid indole alkaloids isolated from the species of the Apocynaceae, Loganiaceae and Rubiaceae plant families. Strictosidine, an alkaloid glucoside, is formed from a single enantiomer of secologanin and tryptamine by enzymic catalysis and with complete diastereoselectivity. It is the exclusive precursor of more than 2200 alkaloids. The configuration of one or more analogous centers of chirality of them is identical, i.e. homochiral, insofar it will be lost or changed in subsequent reactions. Strictosidine exists in a single, most stable conformer of the possible 324 ones. On simple secologanin derivatives it was proved, that the removal of the glucosyl unit by enzyme results, under kinetic control, in the formation of the epimer pair of the primary aglucone. However, proton catalysed hydrolysis gives, under thermodynamic control, the most stable epimer pair of the possible 48 aglucones formed in 368 elementary steps. In the deglucosylation of the strictosidine type compounds, in 2 series, 1 tricyclic, 8 tetracyclic and 16 pentacyclic aglucone types are formed by further oxa-, carba- and/or azacyclizations. The alkaloids derived from strictosidine can be grouped into one unrearranged (I) and two rearranged (II and III) skeletons, in normal and iso series as well as along a and b lines. The processes are directed partially by proton migrations. The really existing alkaloids are formed in subsequent chemical reactions. The rich molecular library obtained by that way reveals the fundamental unity of Nature in the material multiplicity, i.e. it lets shine up the beauty in the world of the biomolecules, too.

Alkaloids↗
PubMed2004

Plasmodium falciparum parasite prevalence in East Africa: a review.

OBJECTIVES: Empirical data on malaria endemicity are rarely available for public domain use to guide effective malaria control. This paper describes the work carried in East Africa since 1997 as part of a pan-African collaboration to map the risk of malaria, Mapping Malaria Risk in Africa (MARA) aimed at redressing deficiency. DATA EXTRACTION: Studies of cross-sectional community estimates of Plasmodium falciparum prevalence among children aged 0-15 years were identified from a variety of sources including electronic searches of published material, manual review of pre-electronic peer reviewed journals and searches of libraries and archives in Kenya, Tanzania and Uganda. Each survey source, infection prevalence, date, longitude and latitude and survey characteristics were recorded. DATA SYNTHESIS: All data were subjected to a number of selection criteria including minimum sample sizes, samples randomly selected, community-based surveys, age ranges of sampled communities within 0-15 years, and surveys that were spatially unique. Of the 2,003 survey data points identified since 1907 in East Africa, only 503 were eligible for inclusion in the analysis dating from 1927 to 2003. The spatial plots of the data demonstrate the paucity of information on malaria prevalence from a number of densely populated areas and highlight the concentration of empirical data in concert with research centres in the sub-region. CONCLUSIONS: Models are required to define malaria risk in areas of East Africa where no empirical data are available so that limited resources can be better targeted to those in greatest need.

Adolescent↗
PubMedDate not supplied

[What can we expect of Collaborative Review Groups of Cochrane Collaboration in neuropaediatrics?].

INTRODUCTION: Cochrane Collaboration (CC) contains detailed, critical and up-to-date systematic reviews (SR) of the best scientific evidence available. AIM: To analyse the bibliometric characteristics of the SR related to paediatric neurology published in the 50 Collaborative Review Groups (CRG) of the CC. MATERIALS AND METHODS: Bibliometric analysis of the Database of Systematic Reviews in Cochrane Library, Issue 2, 2005 (n = 2.231 SR). The variables recorded were: number of SR and protocols in any CRG, authors and clusters of secondary research, dates (late review and update), type of study, critical review of the SR and conclusions. RESULTS: Nine published SR about neuropaediatrics: the Epilepsy Group (24 SR), the Neuromuscular Disease Group (16), the Neonatal Group (16), the Developmental, Psychosocial and Learning Problems Group (10), the Pain, Palliative Care and Supportive Care Group (4), the Movement Disorders Group (3), the Injuries Group (3), the Infectious Disease Group (3) and the Acute Respiratory Infections Group (2). The three main thematic areas were treatment of epilepsy (pharmacologic and non-pharmacologic), neonatal neurology (mainly intraventricular haemorrhage and perinatal asphyxia) and miscellanea (autism spectrum disorder, headache, cerebral palsy, myasthenia gravis, Guillain-Barre syndrome, Bell's palsy and bacterial meningitis). All the SR were about treatment interventions. CONCLUSIONS: Paediatric neurology SR are infrequent (3.6% of the 2.231 SR published in CC), and helps an evidence-based decision-making in a few areas: pharmacologic treatment of epilepsy, management of intraventricular haemorrhage of preterm infants and bacterial meningitis. Many therapies in paediatric neurology persist with no supporting evidence, and we detected no SR about important neurological issues in childhood as attention-deficit hyperactivity disorder, mental retardation and hypotonia.

Bibliometrics↗
PubMed1987

Continuing medical education.

With the rapid advances in medical science and increasing complexities of patient care, the need for continuing medical education (CME) is widely accepted by the profession. CME follows general and higher professional training, and should be a life long process. Teaching hospitals and postgraduate professional institutions play vital roles in organising, promoting, and monitoring this activity. CME directorates should be established. University authorities must recognise the important role of medical teachers in postgraduate and continuing medical education, and the staff establishment and terms of service should be held regularly. Medical libraries should have easy borrowing facilities. Self-assessment and audio-visual material are particularly helpful to the busy practitioner and inexpensive local or regional journals of quality can provide pertinent and up-to-date information. All charges for attending scientific meetings and educational material should be tax deductible or subsidized. The effectiveness of CME is difficult to assess and participation is almost impossible to enforce. Much depends on the standard of medical practice wanted by society. Recertification of general practitioners or specialists poses many problems. On the other hand, completion of self-assessment programmes, active participation at medical meetings, contributions to scientific literature, and membership of medical societies with built-in peer review could be monitored and regularly used to evaluate professional status.

Education, Medical, Continuing↗
PubMed2003

Diversity oriented synthesis and branching reaction pathway to generate natural product-like compounds.

Combinatorial chemistry can be used to synthesize diversified molecules on a large scale. As with all large-scale experiments, this process requires a major investment in equipment, consumables and time. Therefore, careful design is critical. As the complexity of the libraries to be generated increases, additional considerations become important. What are the issues that should be considered when planning combinatorial chemistry projects? Which features in the design strategy are critical to consider ensuring that all of the potential products will be synthesized? How are the reactants selected to optimize product synthesis and yield? Over the last several years, through an experimental process, we have successfully developed and optimized our synthetic strategy. Our approach incorporates a number of critical components into a tightly controlled process that generates molecules with maximal structural complexity. This complexity emanates from carbon-carbon bond formation, which is extremely stable and it is reminiscent of complex natural product molecules. Our studies have illustrated that transition metal catalysts are powerful reagents that can be used to drive the synthesis of diverse small molecules from less complex starting materials. In this review, we will describe some of our recent efforts to synthesize natural product-like molecules and their derivative structures to successfully create libraries of complex molecules for drug discovery applications. Our diversity-oriented synthesis methods incorporate transition metal catalysts, as a versatile tool for creating carbon-carbon bonds and structural complexity, and the branched reaction pathway, as a method for incorporating diversity into the molecular scaffolds. We will review our combinatorial chemistry program, focusing on the decisions that we made for (1) the scaffold selection; (2) the design of a diversity oriented approach for library synthesis; (3) the incorporation of the branched reaction pathway to generate natural product-like molecules from the same starting material; and (4) the process steps that we selected for chemistry development and library generation.

Biological Factors↗
PubMed1988

Selective Medical Library on Microfiche. An international experiment supported by the Rockefeller Foundation.

The Selective Medical Library on Microfiche (SMLM) project is designed to improve access to the world's significant biomedical literature in developing countries' medical school libraries through the provision of a first-rate, low-cost core collection of journals. One hundred and five journals representing thirty-six biomedical specialties were selected using a method designed specifically for SMLM. The journals are provided on microfiche because of its relative low cost, durability, easy reproduction, and rapid delivery by air mail. SMLMs have been established at test and demonstration sites in four medical schools in Egypt, Indonesia, Mexico, and Colombia. SMLMs are delivered as turnkey systems consisting of the microfiche collection, a reader-printer, four fiche readers, necessary furniture, and promotional and training materials. The project involves extensive evaluation.

Developing Countries↗
PubMed1997

Isolation of human ear specific cDNAs and construction of cDNA libraries from surgically removed small amounts of inner ear tissues.

We have used representational difference analysis (RDA) for subtractive hybridization of oligo dT primed directionally cloned cDNA libraries from human inner ear tissue and a B-lymphoblast cell line. Two rounds of subtraction-amplification, followed by differential hybridization of selected clones led to the isolation of genes which were specific to the ear. Sequence analysis of randomly chosen clones revealed the presence of a histidine rich Ca2+ binding protein, human dynamin, collagen type 1A1, collagen type 2A1, SPARC, human growth hormone, and several specific genes which had no sequence homology in the data base. Furthermore, to apply these techniques for isolating genes specific to distinct inner ear structures and/or cell types of inner ear for which the starting tissue material is limiting, we have used a modified PCR based protocol to construct representative cDNA libraries. We have characterized a cDNA library constructed from small amounts of inner ear tissues recovered by ablative surgical procedure involving labyrinthectomy. The potential application of these protocols for isolating genes involved in hearing and deafness is discussed.

Adult↗
PubMed1996

Benchmarking in health care: using the Internet to identify resources.

Benchmarking is a quality improvement tool that is increasingly being applied to the health care field and to the libraries within that field. Using mostly resources assessible at no charge through the Internet, a collection of information was compiled on benchmarking and its applications. Sources could be identified in several formats including books, journals and articles, multi-media materials, and organizations.

Computer Communication Networks↗
PubMed1986

Searching health education literature. Bibliographic and indexing tools.

The first two articles in this series looked in different ways at relationships between libraries and health education units. We now look at a selection of bibliographic and indexing tools that can be used to identify journal articles, books and other materials of interest to health educators. Audio-visual items are not covered.

Information Services↗
PubMed2006

The Bead blot: a method for identifying ligand-protein and protein-protein interactions using combinatorial libraries of peptide ligands.

Small molecules that bind proteins can be used as ligands for protein purification and for investigating protein-protein and protein-drug interactions. Unfortunately, many methods used to identify new ligands to desired proteins suffer from common shortcomings, including the requirement that the target protein be purified and/or the requirement that the ligands be selected under conditions different from those under which it will be used. We have developed a new method called the Bead blot that can (i) select ligands to unpurified proteins, including trace proteins, present in complex materials (e.g., unfractionated plasma); (ii) select ligands to multiple proteins under a variety of conditions in a single experiment; and (iii) be used with libraries of different types of ligands. In the Bead blot, a library of ligands, synthesized on chromatography resin beads, is incubated with a starting material containing a target protein for which a ligand is sought. The proteins in the material bind to their complementary ligands according to specific affinity interactions. Then the protein-loaded beads are immobilized in a porous matrix, and the proteins are directionally eluted from the beads and captured on a membrane superimposed on the beads. The location of the target protein on the membrane is determined, and because the position of the protein(s) on the membrane reflects the position of the bead(s) in the matrix, the bead that originally bound the protein is identified, with subsequent elucidation of the ligand sequence. Ligands to several targets can be identified in one experiment. Here we demonstrate the broad utility of this method by the selection of ligands that purify plasma protein complexes or that remove pathogens from whole blood with very high affinity constants. We also select ligands to a protein based on competitive elution.

Amino Acid Sequence↗
PubMed2001

In vitro protein display in drug discovery.

Nucleic acid-encoded libraries have been used at different stages of the drug discovery process for the identification of polypeptide ligands and for target identification. Traditionally, phage display screening systems have been used to explore large libraries of peptides and proteins. Lately, novel protein selection technologies have been developed that work entirely in vitro and use the polymerase chain reaction (PCR) rather than cells to amplify genetic material. The simplicity of the linkage between the protein and its encoding nucleic acid leads to several advantages, including the use of larger libraries without the biases of cell-based amplification, greater control over binding conditions and the ease with which PCR-based mutagenesis and recombination can be incorporated. This review focuses on the latest improvements in this new generation of in vitro protein display techniques and discusses their applications to the drug discovery process.

Animals↗
PubMed2006

Caries-preventive effect of resin-based and glass ionomer sealants over time: a systematic review.

INTRODUCTION: The difference in preventing dentine lesion development between resin-based and glass ionomer sealant materials is unclear. Two recently published reviews were unable to conclude on the difference because the comparison was an exclusion criterion in one review and there were statistical shortcomings in the relevant papers in the other (Cochrane) review. OBJECTIVES: The aim of the present investigation was to carry out a systematic review on the caries-preventive effect of these two types of sealant materials under more liberal exclusion criteria concerning the statistical presentations in the publications. METHODS: Based on five exclusion criteria, the literature search in the electronic libraries PubMed and MEDLINE and the publications retrieved in the Cochrane review, revealed 12 eligible publications for analyses. A variety of glass ionomers and resin-based sealant materials had been applied in the included studies. Attributable risk (AR) was chosen rather than relative risk (RR), as used in the Cochrane review, because RR is very instable in a low caries population. RESULTS: There was no consistent pattern observed with respect to the caries-preventive effect of either resin-based or glass ionomer sealants. Therefore, it was impossible to calculate an overall AR. CONCLUSIONS: There is no evidence that either resin-based or glass ionomer sealant material is superior to the other in preventing dentine lesion development in pits and fissures over time.

Dental Caries↗