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A comprehensive and critical review of dental implant placement in diabetic animals and patients.

OBJECTIVES: A thorough and exhaustive analysis of the available studies concerning placement of endosseous dental implants in diabetic subjects has not been previously published. The aim of the present study was to perform a comprehensive and critical review of experimental and clinical studies published in the international peer-reviewed literature in the English language regarding endosseous implant installation in diabetic subjects and to draw evidence-based conclusions on the effectiveness and predictability of dental implant therapy in diabetic patients. MATERIAL AND METHODS: Literature search for articles published up to and including March 2005 in the English language was performed with a personal computer (PC) using The National Library Of Medicine (http://www.ncbi.nlm.nih.gov/PubMed) and Cochrane Oral Health Group databases. Search strategy included a specific series of terms and key words. The reference lists of identified publications, relevant texts and previous workshops were also scanned. Data sources also included several hand-searched journals and contact with experts, when it was considered appropriate. Search was conducted independently by the three reviewers (S. K., I. K. K., I. F.). At the first phase of selection the titles and abstracts and at the second phase full papers were screened independently by the three reviewers. Disagreement regarding inclusion of full papers was resolved by discussion among the reviewers. RESULTS: The search provided 227 potentially relevant titles and abstracts. At the first phase of evaluation, 199 publications were rejected based on title and abstract. At the second phase, the full text of the remaining 28 publications was retrieved for more detailed evaluation. These publications included 11 experimental studies and 16 clinical studies (one clinical study corresponded to two publications). Finally, 11 experimental and eight clinical studies were accepted. Clinical studies included four prospective and four retrospective studies. Because of the limited number of available studies and their heterogeneity, focusing on a specific predefined question to be answered by a systematic review was not feasible and therefore no meta-analysis was planned. CONCLUSION: Within the limits of the existing investigations, experimental studies seem to reveal an impaired bone healing response to implant placement in diabetic animals compared with non-diabetic controls, both quantitatively and qualitatively. The majority of clinical studies tend to indicate that diabetes is no contraindication for implant placement, on condition that it remains under metabolic control. However, definitive guidelines with objective criteria, such as type and duration of diabetes and glucosylated hemoglobin levels, need to be established in the future.

Animals↗

Identification and characterization of a human cytomegalovirus gene coding for a membrane protein that is conserved among human herpesviruses.

A rabbit antiserum was raised against envelope material from purified human cytomegalovirus strain AD169. The serum recognized polypeptides 200, 170, 160, 75, 58, and 45 kilodaltons in size. It was used to screen a cDNA library constructed from poly(A)+ RNA from human cytomegalovirus-infected cells in the expression vector lambda gt11. A recombinant bacteriophage expressing cytomegalovirus-specific sequences was identified, and the corresponding gene was mapped to the HindIII R fragment. The gene is transcribed into a late 1.5-kilobase RNA. The nucleotide sequence of the coding region was determined. Computer analysis of the gene product revealed a polypeptide containing multiple potential membrane-spanning domains, representing a type of protein not identified in the envelope of herpesviruses before. The protein shows homology on the amino acid level to hypothetical proteins from reading frames BBRF3 of Epstein-Barr virus, UL10 of herpes simplex virus type 1, and ORF50 of varicella-zoster virus. By using an antiserum raised against procaryote-expressed parts of the cytomegalovirus membrane protein, a 45-kilodalton structural component of the virus was identified as the gene product.

Amino Acid Sequence↗

Linkage and comparative mapping of the locus controlling susceptibility towards E. COLI F4ab/ac diarrhoea in pigs.

In 1995, Edfors-Lilja and coworkers mapped the locus for the E. COLI K88ab (F4ab) and K88ac (F4ac) intestinal receptor to pig chromosome 13 (SSC13). Using the same family material we have refined the map position to a region between the microsatellite markers Sw207 and Sw225. Primers from these markers were used to screen a pig BAC library and the positive clones were used for fluorescent in situ hybridization (FISH) analysis. The results of the FISH analysis helped to propose a candidate gene region in the SSC13q41-->q44 interval. Shotgun sequencing of the FISH-mapped BAC clones revealed that the candidate region contains an evolutionary breakpoint between human and pig. In order to further characterise the rearrangements between SSC13 and human chromosome 3 (HSA3), detailed gene mapping of SSC13 was carried out. Based on this mapping data we have constructed a detailed comparative map between SSC13 and HSA3. Two candidate regions on human chromosome 3 have been identified that are likely to harbour the human homologue of the gene responsible for susceptibility towards E. COLI F4ab/ac diarrhoea in pigs.

Animals↗

'Genetics home reference': helping patients understand the role of genetics in health and disease.

The surge of information generated by the Human Genome Project has left many health professionals and their patients struggling to understand the role of genetics in health and disease. To aid the lay public and health professionals, the US National Library of Medicine developed an online resource called 'Genetics Home Reference' (GHR), located at http://ghr.nlm.nih.gov/. Launched in April 2003, GHR's goal is to help the public interpret the health implications of the Human Genome Project. It bridges the clinical questions of consumers and the rich technical data emerging from the sequenced human genome. The GHR web site is designed for easy navigation among summaries for genetic conditions and the related gene(s) and chromosome(s). This design strategy enhances the user's appreciation of how genes, chromosomes, and conditions are interrelated.

Genetic Diseases, Inborn↗

A model for training the new bioinformationist.

OBJECTIVES: The objectives were to examine the effectiveness of a curriculum designed to increase bioinformatics competencies of librarians with diverse backgrounds and to identify demographic factors that may affect the learning process. METHODS: Sixteen professional staff participated in a 12-week training course consisting of 5 distinct modules: molecular biology, genetic analysis, biotechnology, research literature, and databases. Participants completed a 120-question pretest and an 88-question posttest designed to evaluate the effectiveness of the training. RESULTS: Training was deemed successful as all participants scored higher on the posttest than the pretest. Data analysis was conducted in relation to participant background. Holding a biology degree did not seem to affect posttest results. Years of experience, however, had an impact on final scores in the databases section, as senior team members had greater difficulty learning the material. DISCUSSION: As the need for specialized information in the area of molecular biology and genetics becomes more central for the effectiveness of organizations, it is crucial for libraries to quickly align with those needs by having a clear vision for increasing the skills and competencies of their staff in this subject area. This paper describes an effective model for learning that was developed and tested by the Eskind Biomedical Library.

Biotechnology↗

Interactions between physicians and the pharmaceutical industry: what does the literature say?

OBJECTIVE: To determine the effect of three types of interaction between physicians and the pharmaceutical industry--company-funded clinical trials, company-sponsored continuing medical education (CME) and information for physicians supplied by pharmaceutical detailers--on orientation and quality of clinical trials, content of CME courses and physicians' prescribing behaviour. DATA SOURCES: MEDLINE and HEALTH searches for English-language articles published from 1978 to 1993, supplemented by material from the author's personal collection. STUDY SELECTION: A total of 227 papers from the MEDLINE and HEALTH searches and about 2000 items from the author's library were initially reviewed. The following selection criteria were used: studies conducted in Australia, Canada, New Zealand, Britain and the United States; studies conducted after 1977; quantitative surveys containing details of the survey methods; studies on the orientation and quality of company-funded clinical trials and on the content of CME courses giving explicit criteria used in the evaluation; and reports on the outcome of interactions stating how the outcomes were assessed. Thirty-six studies met these criteria. DATA EXTRACTION: Information was extracted on five topics: physicians' attitudes toward drug industry interactions, frequency with which physicians participate in the interactions, orientation and quality of company-funded clinical trials, content of company-sponsored CME courses and changes in physicians' prescribing behaviour as a result of an interaction. DATA SYNTHESIS: Although most physicians participate only occasionally in company-sponsored clinical trials, most see detailers and attend company-sponsored CME courses. However, physicians do not have a very high opinion of the information from detailers or of company-sponsored CME events. Many doctors regard pharmaceutical companies as an important source of funding for clinical trials, but they also have concerns about accepting money from this source. Company funding of clinical trials may affect the quality of the trials and the types of research that physicians undertake. Company-sponsored CME courses may have a commercial bias even if conducted under guidelines designed to ensure the independence of the event. All three types of interactions affect physicians' prescribing behaviour and, in the case of obtaining information from detailers, physicians' prescribing practices are less appropriate as a result of the interaction. CONCLUSIONS: Physicians are affected by their interactions with the pharmaceutical industry. Further research needs to be done in most cases to determine whether such interactions lead to more or less appropriate prescribing practices. The CMA's guidelines on this topic should be evaluated to see whether they are effective in controlling physician-industry interactions. Further measures may be necessary if the guidelines fail to prevent negative effects on prescribing practices.

Attitude of Health Personnel↗

[Scientific information of health personnel: an approach to the sources, access, costs and research].

OBJECTIVE: To study what general sources of information health professionals working in primary care use, their access to them, expenditure incurred in health information and whether they do research and publish it. DESIGN: A descriptive crossover study using an anonymous questionnaire. SETTING: Primary care. PARTICIPANTS: Doctors, paediatricians, nurses and midwives working in the primary care field in Area 13 of the Community of Valencia. 163 out of 255 people polled replied (63.9% participation). MEASUREMENTS AND MAIN RESULTS: The main sources of information favoured are courses and clinical sessions. 83.5% of professionals had done some course or attended a congress or workshop over the two previous years. 78.9% of staff had needed to look for a book or magazine outside their own library and mainly looked outside the Health Centres. 20.8% spent no money on health information. 34.4% had done research work: 24 doctors and 9 nurses had published. 14.7% felt supported always or often by their health area to do research. 64% did not have a wordprocessor and 71% did not have a library. CONCLUSIONS: The staff surveyed prefer courses and clinical sessions as their sources of information, which might imply little active searching for information. They believe that they need material and information resources for research work, and that incentives must be offered. Workplaces contain few sources of information.

Adult↗

Targeting tumor vasculature with homing peptides from phage display.

Tumor vasculature expresses a number of molecular markers at much lower levels than those seen in the blood vessels of normal tissues, and in some cases, such markers are undetectable. The presence of these markers relates to angiogenesis; the same markers are shared by all blood vessels undergoing angiogenesis. The endothelial cells, pericytes and smooth muscle cells, and the vascular extracellular matrix in angiogenic vessels can each express such markers. Molecularly, they represent vascular growth factor receptors, cell adhesion proteins and their receptors. Screening of phage display libraries for peptides that home to tumor vasculature when injected into mice has recently provided a new tool for analyzing the distinguishing features of tumor vasculature. Tumor-homing peptides isolated in this manner, as well as an antibody against a form of fibronectin expressed in tumor blood vessels, have been found to serve as targeting devices to concentrate drugs and other therapeutic materials to tumors in in vivo models. Such a targeting strategy can therefore potentially improve the efficacy of drugs and reduce their side effects.

Endothelium, Vascular↗

Efficacy of different intraocular lens materials and optic edge designs in preventing posterior capsular opacification: a meta-analysis.

PURPOSE: To evaluate the efficacy of different intraocular lens (IOL) materials and optic edge designs in preventing posterior capsular opacification (PCO). DESIGN: Systematic review and meta-analysis. METHODS: Pertinent studies were selected through an electronic search of the Cochrane Library, MEDLINE, and Embase. The randomized controlled trials meeting the predefined criteria were reviewed systematically by meta-analysis. The treatment effects were measured as risk difference, and the pooled estimates were computed according to a random effect model. RESULTS: In total, 23 randomized controlled trials were included in the present meta-analysis. The pooled risk differences of Nd:YAG laser capsulotomy rates were -24% (95% confidence interval [CI], -29% to -20%) comparing acrylic with polymethylmethacrylate (PMMA) lenses; -9% (95% CI, -17% to -1%) comparing silicone with PMMA lenses; 14% (95% CI, -8% to 36%) comparing hydrogel with PMMA lenses; 4% (95% CI, -2% to 10%) comparing silicone with acrylic lenses; 19% (95% CI, 8% to 30%) comparing hydrogel with acrylic lenses; and 28% (95% CI, 10% to 46%) comparing hydrogel with silicone lenses. The pooled risk differences of PCO rates were -39% (95% CI, -47% to -31%) comparing acrylic with PMMA lenses; -14% (95% CI, -29% to 0%) comparing silicone with acrylic lenses; 56% (95% CI, 36% to 75%) comparing hydrogel with acrylic lenses; and 48% (95% CI, 31% to 64%) comparing hydrogel with silicone lenses. When comparing sharp with rounded-edge designs, pooled risk differences of capsulotomy rates were -47% (95% CI, -77% to -17%) in PMMA lenses, -22% (95% CI, -47% to 2%) in acrylic lenses, and -9% (95% CI, -17% to 0%) in silicone lenses; pooled risk differences of PCO rates were -28% (95% CI, -50% to -7%) in acrylic lenses and -37% (95% CI, -46% to -27%) in silicone lenses. CONCLUSIONS: The rates of PCO and Nd:YAG laser capsulotomy may be influenced by different IOL biomaterials and optic edge designs. The lenses made by acrylic and silicone and those with sharp optic edges are superior in lowering the rates of PCO and laser capsulotomy.

Acrylic Resins↗

Generation of new protein kinase inhibitors utilizing cytochrome p450 mutant enzymes for indigoid synthesis.

Indigoids, a class of bis-indoles, represent a promising protein kinase inhibitor scaffold. Oxidation of indole by cytochrome P450 (P450) has been shown to generate species (indoxyl, isatin) that couple to yield indigo and indirubin. Escherichia coli-expressed human P450 2A6 mutants isolated from a randomized library were incubated with 27 substituted indole derivatives. Extracts of the cultures were screened for inhibition of human cyclin-dependent kinases (CDK)-1 and -5 and glycogen synthase kinase-3 (GSK3). The extracts from cultures incubated with 5-methoxyindole were the most inhibitory. High-performance liquid chromatography (HPLC) separation yielded a mixture of seven colored indigoids. These indigoids included indigo, indirubin, the di(5-methoxy) derivatives of indigo and indirubin, and both of the possible mono 5-methoxy derivatives of indirubin, which were all identified by visible, mass, and NMR spectra. Cultures with 5-methylindole added to the media also yielded inhibitory material, and 5- and 5'-methylindirubin were characterized. The most inhibitory of these indigoids were the monosubstituted indirubins and 5,5'-dimethoxyindirubin, which was > or =10x more active than indirubin. Thus, the overall approach involves the use of a library of randomized enzyme mutants to activate component moieties of a desired set of larger molecules, thus yielding a library of drug candidates that can be screened and characterized. The general strategy may have additional applications.

Aryl Hydrocarbon Hydroxylases↗

Development of a system to evaluate compound identity, purity, and concentration in a single experiment and its application in quality assessment of combinatorial libraries and screening hits.

The development and use of a new assay system for the simultaneous determination of identity, purity, and concentration of sample components from combinatorial libraries produced by parallel synthesis are described. The system makes use of high-performance liquid chromatography with UV/vis photodiode array (PDA), evaporative light scattering (ELSD), chemiluminescent nitrogen (CLND), and time-of-flight mass spectrometer (TOFMS) detectors (HPLC-PDA-ELSD-CLND-TOFMS). Although these detectors have previously been utilized separately for the analysis of combinatorial chemistry libraries, the use of TOFMS along with CLND provides a synergistic combination enabling target and side-product structures to be identified and their concentrations and purities determined in a single experiment from a solution containing microgram levels of material. The CLND was found to give a linear response based on the number of moles of nitrogen present. Therefore, if the number of nitrogens per molecule is known, the concentration of each nitrogen-containing sample component may be determined utilizing an unrelated co-injected standard. A molecular formula for an impurity may often be calculated from the exact mass determined by the TOFMS and knowledge of the chemistry involved. Thus, if the sample components contain nitrogen, the concentration of every identified HPLC peak may be determined even in the absence of primary standards. This combination of detectors enabled the characterization of both target compounds and byproducts in combinatorial libraries, allowing the optimization of library synthetic procedures. This system was also used to survey the quality of libraries, enabling the selection of the best libraries for screening. This method also facilitated the characterization of samples from combinatorial libraries found as hits in high-throughput screening to establish the potency of the leads based on their actual concentration. In addition, concentrations and potencies of impurities were determined after identification of their structures, utilizing exact mass data, determination of charge states, and knowledge of the synthetic chemistry.

Journal Article↗

Cell-specific targeting of nanoparticles by multivalent attachment of small molecules.

Nanomaterials with precise biological functions have considerable potential for use in biomedical applications. Here we investigate whether multivalent attachment of small molecules can increase specific binding affinity and reveal new biological properties of such nanomaterials. We describe the parallel synthesis of a library comprising 146 nanoparticles decorated with different synthetic small molecules. Using fluorescent magnetic nanoparticles, we rapidly screened the library against different cell lines and discovered a series of nanoparticles with high specificity for endothelial cells, activated human macrophages or pancreatic cancer cells. Hits from the last-mentioned screen were shown to target pancreatic cancer in vivo. The method and described materials could facilitate development of functional nanomaterials for applications such as differentiating cell lines, detecting distinct cellular states and targeting specific cell types.

Animals↗

Efficacy of homeopathic arnica: a systematic review of placebo-controlled clinical trials.

BACKGROUND: The efficacy of homeopathic remedies has remained controversial. The homeopathic remedy most frequently studied in placebo-controlled clinical trials is Arnica montana. OBJECTIVE: To systematically review the clinical efficacy of homeopathic arnica. MATERIALS AND METHODS: Computerized literature searches were performed to retrieve all placebo-controlled studies on the subject. The following databases were searched: MEDLINE, EMBASE, CISCOM, and the Cochrane Library. Data were extracted in a predefined, standardized fashion independently by both authors. There were no restrictions on the language of publications. RESULTS: Eight trials fulfilled all inclusion criteria. Most related to conditions associated with tissue trauma. Most of these studies were burdened with severe methodological flaws. On balance, they do not suggest that homeopathic arnica is more efficacious than placebo. CONCLUSION: The claim that homeopathic arnica is efficacious beyond a placebo effect is not supported by rigorous clinical trials.

Arnica↗

The treatment of depression in cancer patients: a systematic review.

GOALS OF THE WORK: To evaluate the efficacy of pharmacological and nonpharmacological treatments for depression in cancer populations. MATERIALS AND METHODS: The Supportive Care Guidelines Group conducted a systematic review of the published literature through June 2005. Search sources includes MEDLINE, EMBASE, CINAHL, PsycInfo, and the Cochrane Library. Comparative studies of treatments for depression in cancer patients were selected for review by two group members based on predefined criteria. MAIN RESULTS: Seven trials of pharmacological agents and four of nonpharmacological interventions were identified. Two trials detected a significant reduction in depressive symptoms for mianserin compared with placebo, and one trial found alprazolam to be superior to progressive muscle relaxation. Four drug trials found no significant difference between groups on depression measures although posttreatment reduction of symptoms was observed for all groups in two trials comparing active treatments (fluoxetine vs desipramine and paroxetine vs amitriptyline). Of the four trials involving nonpharmacological therapies for the management of depression, two detected a benefit for treatment (a multicomponent nurse delivered intervention and an orientation program) over usual care. CONCLUSION: There is limited evidence for the effectiveness of pharmacological and psychosocial interventions in the treatment of cancer patients with depressive disorders, and no evidence for the superiority of one treatment modality over another. Based on evidence from the general population and other medically ill populations, combined approaches to the treatment of depression may be the most effective. Further research is necessary in cancer patients to determine the relative effectiveness of psychosocial, pharmacological, and combined treatments.

Antidepressive Agents↗

Identification and analysis of unsatisfactory psychosocial work situations: a participatory approach employing video-computer interaction.

A method for psychosocial evaluation of potentially stressful or unsatisfactory situations in manual work was developed. It focuses on subjective responses regarding specific situations and is based on interactive worker assessment when viewing video recordings of oneself. The worker is first video-recorded during work. The video is then displayed on the computer terminal, and the filmed worker clicks on virtual controls on the screen whenever an unsatisfactory psychosocial situation appears; a window of questions regarding psychological demands, mental strain and job control is then opened. A library with pictorial information and comments on the selected situations is formed in the computer. The evaluation system, called PSIDAR, was applied in two case studies, one of manual materials handling in an automotive workshop and one of a group of workers producing and testing instrument panels. The findings indicate that PSIDAR can provide data that are useful in a participatory ergonomic process of change.

Computers↗

The contribution of molecular biology to the development of vaccines against nematode and trematode parasites of domestic ruminants.

Rapid developments in molecular biology have had an enormous impact on the prospects for the development of vaccines to control the major nematode and trematode infestations of livestock. Vaccine candidates are purified using conventional protein chemistry techniques but the limitations imposed by the scarcity of parasite material provide an insurmountable barrier for commercial vaccine production by this means. The ability to purify mRNA from different parasite life-cycle stages and to prepare cDNA expression libraries from it has proven central to the identification of immunogenic parasite proteins. Potentially, protective parasite antigens can now be produced in recombinant form in a variety of vectors and this represents a key breakthrough on the road to commercial vaccine production. The contribution of molecular biology to this process is discussed using several examples, particularly in vaccine development against the pathogenic abomasal nematode of sheep and goats, Haemonchus contortus, and the liver fluke of sheep and cattle, Fasciola hepatica. The difficulties of producing recombinant proteins in the correct form, with appropriate post-translational modification and conformation, are discussed as well as emerging means of antigen delivery including DNA vaccination. The opportunities offered by genome and expressed sequence tag analyses programmes for antigen targeting are discussed in association with developing microarray and proteomics technologies which offer the prospect of large scale, rapid antigen screening and identification.

Animals↗

Thresholds for human detection of patient setup errors in digitally reconstructed portal images of prostate fields.

PURPOSE: Computer-assisted methods to analyze electronic portal images for the presence of treatment setup errors should be studied in controlled experiments before use in the clinical setting. Validation experiments using images that contain known errors usually report the smallest errors that can be detected by the image analysis algorithm. This paper offers human error-detection thresholds as one benchmark for evaluating the smallest errors detected by algorithms. Unfortunately, reliable data are lacking describing human performance. The most rigorous benchmarks for human performance are obtained under conditions that favor error detection. To establish such benchmarks, controlled observer studies were carried out to determine the thresholds of detectability for in-plane and out-of-plane translation and rotation setup errors introduced into digitally reconstructed portal radiographs (DRPRs) of prostate fields. METHODS AND MATERIALS: Seventeen observers comprising radiation oncologists, radiation oncology residents, physicists, and therapy students participated in a two-alternative forced choice experiment involving 378 DRPRs computed using the National Library of Medicine Visible Human data sets. An observer viewed three images at a time displayed on adjacent computer monitors. Each image triplet included a reference digitally reconstructed radiograph displayed on the central monitor and two DRPRs displayed on the flanking monitors. One DRPR was error free. The other DRPR contained a known in-plane or out-of-plane error in the placement of the treatment field over a target region in the pelvis. The range for each type of error was determined from pilot observer studies based on a Probit model for error detection. The smallest errors approached the limit of human visual capability. The observer was told what kind of error was introduced, and was asked to choose the DRPR that contained the error. Observer decisions were recorded and analyzed using repeated-measures analysis of variance. RESULTS: The thresholds of detectability averaged over all observers were approximately 2.5 mm for in-plane translations, 1.6 degrees for in-plane rotations, 1 degrees for out-of-plane rotations, and 8% change in magnification for out-of-plane translations along the central axis. When one inexperienced observer is excluded, the average threshold for change in magnification is 5%. Experienced observers tended to perform better, but differences between groups were not statistically significant. Thresholds were computed as averages over all observers. Because of the broad range of observer capabilities, some detection tasks were too difficult for some observers, leading to missing threshold values in our data analysis. The missing values were excluded from computation of the average thresholds reported above. The effect of the missing values is to bias the average values toward the best human performance. CONCLUSIONS: Under favorable conditions, humans can detect small errors in setup geometry. The thresholds for error detection reported in this study are believed to represent rigorous but reasonable benchmarks that can be incorporated into studies evaluating algorithms for computer-assisted detection of setup errors in electronic portal images.

Diagnostic Errors↗

The virtual laboratory: a new on-line resource for the history of psychology.

The authors provide a description of the Virtual Laboratory at Department III of the Max Planck Institute for the History of Science in Berlin. The Virtual Laboratory currently provides Internet links to rooms that present texts, instruments, model organisms, research sites, and biographies. Existing links provide access to a library of journals, handbooks, monographs, and trade catalogues; research institutes and laboratories; biographies and bibliographic essays; and essays by contemporary researchers. Historians of psychology are encouraged to submit photographic material and essays to the Virtual Laboratory.

Europe↗