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Montage: a system for three-dimensional reconstruction by personal computer.

This paper describes a simplified system for serial section three-dimensional (3-D) reconstruction. A set of 9 software programs runs on a standard personal computer and produces camera-ready illustrations suitable for publication. The user enters trace points on a digitizing tablet from sections that have been already aligned. A 3-D view of the reconstructed object is generated which can be displayed with hidden lines removed. Analysis of volume, surface area and autoradiographic grain density are performed automatically. A relational database query language allows display and analysis of a selected subset of the data. The system runs under the UNIX operating system which allows the programs to be easily transported to new hardware or modified for other purposes.

Animals↗

Genomic cartography of varicella-zoster virus: a complete genome-based analysis of strain variability with implications for attenuation and phenotypic differences.

In order to gain a better perspective on the true variability of varicella-zoster virus (VZV) and to catalogue the location and number of differences, 11 new complete genome sequences were compared with those previously in the public domain (18 complete genomes in total). Three of the newly sequenced genomes were derived from a single strain in order to assess variations that can occur during serial passage in cell culture. The analysis revealed that while VZV is relatively stable genetically it does posses a certain degree of variability. The reiteration regions, origins of replication and intergenic homopolymer regions were all found to be variable between strains as well as within a given strain. In addition, the terminal viral sequences were found to vary within and between strains specifically at the 3' end of the genome. Analysis of single nucleotide polymorphisms (SNPs) identified a total of 557 variable sites, 451 of which were found in coding regions and resulted in 187 different in amino acid substitutions. A comparison of the SNPs present in the two gE mutant strains, VZV-MSP and VZV-BC, suggested that the missense mutation in gE was primarily responsible for the accelerated cell spread phenotype. Some of the variations noted with high passage in cell culture are consistent with variations seen in the IE62 gene of the vaccine strains (S628G, R958G and I1260V) that may help in pinpointing variations essential for attenuation. Although VZV has been considered to be one of the most genetically stable human herpesviruses, this initial assessment of genomic VZV cartography provides insight into ORFs with previously unreported variations.

Base Sequence↗

Evaluation of inactivated hepatitis A vaccine in Canadians 40 years of age or more.

OBJECTIVE: To assess the side effects and immune responses after three serial doses of a new inactivated hepatitis A vaccine in people 40 years of age or more. DESIGN: Open, noncomparative trial. SETTING: A hospital, a regional laboratory and public health units in British Columbia. PARTICIPANTS: A volunteer sample of 64 healthy adults aged 40 to 61 years who were seronegative for hepatitis A virus (HAV). All were staff or associates of the health facilities. Exclusion criteria included elevated serum alanine and aspartate aminotransferase levels, a history of liver disease and recent travel to areas of high risk for HAV infection. INTERVENTION: A formalin-inactivated, alum-adsorbed vaccine containing 720 ELISA (enzyme-linked immunosorbent assay) units of antigen from HAV strain HM175 per 1.0-mL dose was injected intramuscularly into the delgoid area. The second and third doses were given 1 and 6 months later respectively. MAIN OUTCOME MEASURES: A detailed diary of any adverse effects for 3 days after each dose. HAV antibody levels in blood samples taken before and 30 days after each dose. RESULTS: All subjects completed the planned series of vaccinations and blood tests; symptom diaries were returned after 190 (99%) of 192 vaccinations. Local symptoms, most often soreness, were reported after 46% of the vaccinations but were mild and usually resolved within 24 hours. A temperature of more than 38.0 degrees C was never reported. Seroconversion occurred in all cases after the two primary doses, and the subjects were still seropositive at 6 months. After the booster dose the geometric mean titre was 2380 mIU/mL, all values being 200 mIU/mL or greater. CONCLUSION: In healthy adults 40 years of age or more the HAV vaccine was well tolerated and highly immunogenic. Final antibody levels were much higher than reported in people passively immunized against HAV with immune serum globulin.

Adult↗

Cytoarchitectonics of the human nucleus accumbens.

More than 400 publications per year deal with the Nucleus accumbens, however its morphological substrate and anatomical borders appear arbitrary. With a modified Nissi-technique applied to complete sets of thick serial, frontoparallel sections, it became possible to characterize the human Nucleus accumbens. In two series a clear delineation of its borders is documented. Along its rostro-caudal axis, the Nucleus accumbens shows morphological differences: the rostral Nucleus accumbens exhibits a higher cell-density and basophilia than Nucleus caudatus and Putamen; in caudal planes, the Nucleus accumbens dissolves into cell-clusters. A hitherto unrecognized supracommissural part of the Nucleus accumbens dorsal to the Commissura anterior is contiguous to the medial and lateral parts of the Nucleus interstitialis striae terminalis. The thickness of the hemispheric slices (approximately 600 micrometers) facilitated the topographical unravelling of the surrounding cell-islands. In accordance with Sanides (1957) these islands were referred to as Insulae terminales. Based on their topography and cellular structure, they were termed insulae terminales subputaminales (ltsp), Insulae terminales nuclei accumbentis (Itna), Insulae terminales supracommissurales (Itsc) and Insulae terminales olfactoriae mediales et laterales (Itom, Itol). The Insulae terminales form an almost complete envelope around the human Nucleus accumbens and could correspond to the neurochemically defined accumbal shell-region of the rat. Marked differences between medial and lateral insulae terminales olfactoriae permit a clear delineation between the human Nucleus accumbens and the lateral, rudimentary Tuberculum olfactorium: the basis for modifying the concept of a ventral striatum in man.

Adult↗

The frequency of uterine leiomyomas.

As a leading cause of hysterectomy in premenopausal women. uterine leiomyomas are a major public health problem. However, very little work has been done on their epidemiology. Indeed, their true frequency has never been established using systematic and meticulous methods. In this study, gross serial sectioning at 2-mm intervals was applied as an adjunct to routine pathology processing in 100 consecutive total hysterectomy specimens. This tripled the number of leiomyomas noted in routine pathology reports. There were 649 leiomyomas in 77 of 100 uteri, with multiplicity of leiomyomas in 84%. Although leiomyomas were more numerous and larger in women with a clinical diagnosis of myomatous uterus, the incidence was no higher than in uteri removed for other reasons. The postmenopausal incidence of leiomyomas was no lower than the premenopausal incidence, although postmenopausal leiomyomas were smaller and fewer. These findings suggest that epidemiologic studies of leiomyomas may not be valid if they are based only on clinical diagnoses or routine pathology reports.

Adult↗

Accuracy of reporting of methicillin-resistant Staphylococcus aureus in a provincial quality control program: a 9-year study.

We report the results of a province-wide quality control program in which five methicillin-resistant Staphylococcus aureus strains were circulated to all Ontario laboratories (hospital, private, and public health laboratories) on nine occasions between 1980 and 1989. The level of expression of methicillin resistance in each of the isolates was determined by performing viable colony counts on serial dilutions of methicillin in agar, and each isolate was assigned to an expression class according to previous published criteria (A. Tomasz, S. Nachman, and H. Leaf, Antimicrob. Agents Chemother. 35:124-129, 1991). Over this time there was an improvement in the performance of laboratories in the recognition of three strains that were relatively easy to detect (strains B, C, and E). These strains were of expression class II, and 98% of laboratories reported correct identifications in 1986. Performance in identifying two strains (strains A and D) of expression class I remained poor. Strain A was circulated in two surveys in 1987 and 1989, and laboratories were sent a questionnaire requesting details of the methods used in those two surveys. The methods used by the laboratories were classified into three categories: disk diffusion, single-plate screening by agar incorporation, and automated methods, which included premanufactured MIC panels. Between the 1987 and 1989 surveys, there was no change in the performance of the disk diffusion test (60% correct on both occasions), but there was improvement in the sensitivity of the agar incorporation test (36% correct in 1987 and 84% correct in 1989) and in automated methods (43% correct in 1987 and 79% correct in 1989). Over a decade, there was overall improvement in the performance of laboratories in detecting easy-to-detect strains, but there were difficulties in detecting organisms of low expression class, and an organism of very low expression class should be designated as a control organism for routine testing of methicillin-resistant s. aureus isolates.

Data Collection↗

Falls and consequent injuries in hospitalized patients: effects of an interdisciplinary falls prevention program.

BACKGROUND: Patient falls in hospitals are common and may lead to negative outcomes such as injuries, prolonged hospitalization and legal liability. Consequently, various hospital falls prevention programs have been implemented in the last decades. However, most of the programs had no sustained effects on falls reduction over extended periods of time. METHODS: This study used a serial survey design to examine in-patient fall rates and consequent injuries before and after the implementation of an interdisciplinary falls prevention program (IFP) in a 300-bed urban public hospital. The population under study included adult patients, hospitalized in the departments of internal medicine, geriatrics, and surgery. Administrative patient data and fall incident report data from 1999 to 2003 were examined and summarized using frequencies, proportions, means and standard deviations and were analyzed accordingly. RESULTS: A total of 34,972 hospitalized patients (mean age: 67.3, SD +/- 19.3 years; female 53.6%, mean length of stay: 11.9 +/- 13.2 days, mean nursing care time per day: 3.5 +/- 1.4 hours) were observed during the study period. Overall, a total of 3,842 falls affected 2,512 (7.2%) of the hospitalized patients. From these falls, 2,552 (66.4%) were without injuries, while 1,142 (29.7%) falls resulted in minor injuries, and 148 (3.9%) falls resulted in major injuries. The overall fall rate in the hospitals' patient population was 8.9 falls per 1,000 patient days. The fall rates fluctuated slightly from 9.1 falls in 1999 to 8.6 falls in 2003. After the implementation of the IFP, in 2001 a slight decrease to 7.8 falls per 1,000 patient days was observed (p = 0.086). The annual proportion of minor and major injuries did not decrease after the implementation of the IFP. From 1999 to 2003, patient characteristics changed in terms of slight increases (female gender, age, consumed nursing care time) or decreases (length of hospital stay), as well as the prevalence of fall risk factors increased up to 46.8% in those patients who fell. CONCLUSION: Following the implementation of an interdisciplinary falls prevention program, neither the frequencies of falls nor consequent injuries decreased substantially. Future studies need to incorporate strategies to maximize and evaluate ongoing adherence to interventions in hospital falls prevention programs.

Accidental Falls↗

A public database for gene expression in human cancers.

A public database, SAGEmap, was created as a component of the Cancer Genome Anatomy Project to provide a central location for depositing, retrieving, and analyzing human gene expression data. This database uses serial analysis of gene expression to quantify transcript levels in both malignant and normal human tissues. By accessing SAGEmap (http://www.ncbi.nlm.nih.gov/SAGE) the user can compare transcript populations between any of the posted libraries. As an initial demonstration of the database's utility, gene expression in human glioblastomas was compared with that of normal brain white matter. Of the 47,174 unique transcripts expressed in these two tissues, 471 (1.0%) were differentially expressed by more than 5-fold (P<0.001). Classification of these genes revealed functions consistent with the biological properties of glioblastomas, in particular: angiogenesis, transcription, and cell cycle related genes.

Brain↗

Within-host competition in genetically diverse malaria infections: parasite virulence and competitive success.

Humans and animals often become coinfected with pathogen strains that differ in virulence. The ensuing interaction between these strains can, in theory, be a major determinant of the direction of selection on virulence genes in pathogen populations. Many mathematical analyses of this assume that virulent pathogen lineages have a competitive advantage within coinfected hosts and thus predict that pathogens will evolve to become more virulent where genetically diverse infections are common. Although the implications of these studies are relevant to both fundamental biology and medical science, direct empirical tests for relationships between virulence and competitive ability are lacking. Here we use newly developed strain-specific real-time quantitative polymerase chain reaction protocols to determine the pairwise competitiveness of genetically divergent Plasmodium chabaudi clones that represent a wide range of innate virulences in their rodent host. We found that even against their background of widely varying genotypic and antigenic properties, virulent clones had a competitive advantage in the acute phase of mixed infections. The more virulent a clone was relative to its competitor, the less it suffered from competition. This result confirms our earlier work with parasite lines derived from a single clonal lineage by serial passage and supports the virulence-competitive ability assumption of many theoretical models. To the extent that our rodent model captures the essence of the natural history of malaria parasites, public health interventions which reduce the incidence of mixed malaria infections should have beneficial consequences by reducing the selection for high virulence.

Animals↗

[Radial hemolysis reaction in the diagnosis of tick-borne encephalitis].

A test of radial hemolysis in gel (RHG) has been developed and first used for serodiagnosis of tick-borne encephalitis (TBE). In examinations of 464 blood serum specimens from 258 patients with TBE and subjects suspected of this disease in RHG and HI tests the diagnosis of tick-borne encephalitis was confirmed in 77 subjects, the results of both tests being in complete agreement. A comparative analysis of antibody levels by RHG and HI tests revealed a complete correlation. An advantage of RHG over HI test is its insensitivity to serum inhibitors and the possibility of quantitation of antibodies in whole sera which omits a complicated procedure of serum treatment to remove inhibitors and serum titrations in serial dilutions mandatory for HI tests. The specificity and sensitivity of RHG, simplicity in running and the possibility of analysing many sera within a short time recommend the RHG test for public health practice for TBE serodiagnosis.

Antibodies, Viral↗

Publishing trends in Chinese medicine and related subjects documented in WorldCat.

BACKGROUND: Chinese medicine (CM) has been the subject of increasing interest in the past 30 years, both as a discipline and in the larger context of alternative medicine. It has steadily been accepted by and integrated into the medical and health-care fields in many countries. OBJECTIVE: This study aims to gain an overview of how CM has been interpreted and presented to the world outside China and to identify emerging trends. METHODS: This study is designed to analyse the publishing trends of CM and related subjects in all languages except Chinese, ranging from books and serials to audio-visual and electronic resources found in WorldCat, the world's largest bibliographic database produced by OnLine Computer Library Center (OCLC). RESULTS: The findings showed a flourishing growth of publications in CM and related subjects beginning in the 1970s with greater coverage on acupuncture. The materials in English language constitute the major portion of total output. CONCLUSION: We conclude that Chinese medicine has steadily gained recognition in the world based on the analysis of publication records. The translation of original works and analysis of journal literature and conference proceedings on Chinese medicine merit further study.

Acupuncture↗

The atopic dog model: report of an attempt to establish a colony.

In an attempt to establish a colony of atopic dogs as a research resource, dogs with seasonal dermatitis - a reported manifestation of naturally occurring allergy in that species - were identified, acquired, and inbred. Progeny were studied during their first 2 years of life to determine if the trait could be genetically transmitted and to investigate the hypothesis that this spontaneously occurring dermatitis correlates with positive laboratory measurements for specific IgE to airborne allergens. (Serial immunoglobulin levels, including total IgE, end-point titration of histamine, and results of fecal examinations for identification of parasites were also investigated and are to be the subject of a separate publication.) Only a weak correlation between positive direct skin test results and the appearance of seasonal dermatitis was found in initial studies. Neither the results of testing by passive cutaneous anaphylaxis nor radioallergosorbent procedures correlated with positive clinical findings. Independently conducted clinical examinations and direct skin testing using selected antigens, as well as additional bronchial challenges of representative animals from the colony, also failed to furnish evidence of atopy in the dogs. Therefore, the goal of establishing an inbred line of atopic animals was not accomplished within the allotted 2-year period. Also, the data did not show a positive correlation between the seasonal dermatitis and measurements for specific IgE to airborne allergens.

Animals↗

Critical review and meta-analysis of serial agitated dilutions in experimental toxicology.

1. We conducted an overview and quantitative meta-analysis of all experimental literature on the protective effects of serial agitated dilutions (SADs) of toxin preparations. 2. Articles were systematically collected and evaluated for scientific quality using pre-defined methodological criteria and then independently analysed for validity. 3. We found 105 publications exploring the effects of SAD preparations in toxicological systems. 4. The quality of evidence in these studies was low with only 43% achieving one half of the maximum possible quality score and only 31% reported in a fashion that permitted reevaluation of the data. 5. Very few studies were independently replicated using comparable models. 6. Among the high quality studies, positive effects were reported 50% more often than negative effects. 7. Four of 5 outcomes meeting quality and comparability criteria for meta-analysis showed positive effects from SAD preparations. 8. Average percent protection over controls in these preparations was 19.7 (95%Cl 6.2-33.2). 9. Further research with special attention to methodological detail and independent replication should be done.

Animals↗

Histiocytosis X involving the thyroid and hypothalamus.

A case of histiocytosis X involving the thyroid and hypothalamus is reported. A 16 year old female presented with amenorrhoea and diabetes insipidus. She subsequently developed a painful goitre with biochemical hypothyroidism, and stridor. The stridor and goitre responded to cyclophosphamide. Previous publications on the use of cytotoxics in histiocytosis X involving the thyroid are reviewed. We describe for the first time both the ultrasound appearances of the thyroid in this condition and the use of serial volumetric measurements to monitor therapy.

Adolescent↗

Electronic journals: are they a paradigm shift?

Ejournals are becoming an accepted and necessary means of meeting the demands for the dissemination of knowledge. This introductory article discusses the recent "explosion" of ejournals and provides an explanation of what is meant by an "ejournal." Ejournals are explored within the traditional context of scholarship and a discussion of the "serials crisis" that promoted the inception of ejournals is presented. After laying the groundwork for discussing scholarship in this new age of dissemination of scholarly information, the article discusses whether this digital form of publication can be called a "paradigm shift" in Kuhn's (1970) traditional sense of the word.

Periodicals as Topic↗

NCBI GEO: mining millions of expression profiles--database and tools.

The Gene Expression Omnibus (GEO) at the National Center for Biotechnology Information (NCBI) is the largest fully public repository for high-throughput molecular abundance data, primarily gene expression data. The database has a flexible and open design that allows the submission, storage and retrieval of many data types. These data include microarray-based experiments measuring the abundance of mRNA, genomic DNA and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. GEO currently holds over 30,000 submissions representing approximately half a billion individual molecular abundance measurements, for over 100 organisms. Here, we describe recent database developments that facilitate effective mining and visualization of these data. Features are provided to examine data from both experiment- and gene-centric perspectives using user-friendly Web-based interfaces accessible to those without computational or microarray-related analytical expertise. The GEO database is publicly accessible through the World Wide Web at http://www.ncbi.nlm.nih.gov/geo.

Animals↗

Evolution of a strain of CJD that induces BSE-like plaques.

Bovine spongiform encephalopathy (BSE) has become a public health issue because a recently evolved BSE agent has infected people, yielding an unusual form of Creutzfeld-Jakob disease (CJD). A new CJD agent that provokes similar amyloid plaques and cerebellar pathology was serially propagated. First-passage rats showed obvious clinical signs and activated microglia but had negligible PrP-res (the more protease-resistant form of host PrP) or cerebellar lesions. Microglia and astrocytes may participate in strain selection because the agent evolved, stabilized, and reproducibly provoked BSE-like disease in subsequent passages. Early vacuolar change involving activated microglia and astrocytes preceded significant PrP-res accumulation by more than 50 days. These studies reveal several inflammatory host reactions to an exogenous agent.

Amyloid beta-Protein Precursor↗

[Changes of methicillin-resistant Staphylococcus aureus (MRSA) phagotypes in Gdansk in 1990-1998].

The aim of the study was the assessment of changes in the occurrence of various MRSA phagotypes in hospitals in the Gdańsk area in 1990-1998. The study was carried out on 175 MRSA strains: 45 strains isolated in 1990-1995 and 130 in 1997-1998. The studied staphylococci were obtained from various clinical materials from patients in 18 hospitals. Phagotyping was done with a set of 10 experimental phages from MRSA strains obtained from the Central Public Health Laboratory in London. Drug-resistance was determined by the disc-diffusion method and in case of strains with medium susceptibility to fusidic acid the minimal inhibitory concentration (MIC) was determined by serial dilutions on solid medium. The study showed among MRSA strains isolated in 1997-1998 a new, previously not known strains with phage pattern MR25/M5 predominated (57.7%). Its presence was found in various hospitals in that area. MRSA belonging to MR25/M5 phagotype were mostly resistant to doxycycline, gentamycin, erythromycin, clindamycin, ciprofloxacin, rifampicin and were resistant or only had medium susceptibility to fusidic acid. The MIC values for strains with medium susceptibility to fusidic acid (4-8 micrograms/ml) showed an evident decrease of the susceptibility to this antibiotic, formerly common in MRSA. At the same time, in 1997-1998 a considerable decrease was observed of the number of MRSA strains belonging to MR8/MR12/MR25/30/33/38/M5/622 phagotype (from 31.1% to 0.8%), and disappearance of strains with phagotypes MR25/56B/M3 and MR8/MR25/622, which in 1990-1995 accounted for 15.6% of the studied staphylococci.

Bacteriophage Typing↗