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Biomedical subjects

K Oliver

Publications and source records attributed to K Oliver.

At least 19 recordsLinked to original sources

Prevalence and predictors of osteoporosis treatment in nursing home residents with known osteoporosis or recent fracture.

SUMMARY: We studied nursing home residents with osteoporosis or recent fracture to determine the frequency and predictors of osteoporosis treatment. There was wide variation in performance, and both clinical and systems variables predicted use. This study shows that improvement in osteoporosis care is possible and important for many nursing homes. INTRODUCTION: We determined the prevalence and predictors of osteoporosis evaluation and treatment in high-risk nursing home residents. METHODS: We identified 67 nursing facilities in North Carolina and Arizona with > 10 residents with osteoporosis or recent hip fracture. Medical records (n=895) were abstracted for osteoporosis evaluation [dual-energy X-ray absorptiometry (DXA), vitamin D level, serum calcium), treatment (calcium, vitamin D, osteoporosis medication, hip protectors), clinical, and systems covariates. Data were analyzed at the facility level using mixed models to account for the complex nesting of residents within providers and nursing facilities. RESULTS: Calcium and vitamin D was prescribed for 69% of residents, bisphosphonates for 19%, calcitonin for 14%, other pharmacologic therapies for 6%, and hip protectors for 2%. Overall, 36% received any bone protection (medication or hip protectors), with wide variation among facilities (0-85%). Factors significantly associated with any bone protection included female gender [odds ratio (OR) 2.4, (1.5-3.7)] and nonurban/suburban location [1.5, (1.1-2.2)]. Residents with esophagitis, peptic ulcer disease (PUD), or dysphagia [0.6, (0.4-0.9)] and alcohol abuse [0.2, (0.0-0.9)] were less likely to receive treatment. CONCLUSIONS: There is substantial variation in the quality of osteoporosis treatment across nursing homes. Interventions that improve osteoporosis quality of care are needed.

Aged↗

Investigation of interleukin 10, 12 and 18 levels in patients with head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy. It is the most common neoplasm arising in the upper aerodigestive tract. Interleukin (IL) 12 and IL-18 are cytokines which have a major anti-tumour activity via stimulation of a T-helper type 1 (Th1) immune response. Interleukin 10, a potent antagonist of IL-12, is a cytokine which possesses immunosuppressive activity mainly produced via T-helper type 2 (Th2) cells. Studies of other types of cancer have shown that the level of IL-12 in serum or tissues is suppressed and/or the IL-10 level is increased, suggesting that there is an impaired cell-mediated anti-tumour response. The aim of this study was to measure pre-operative serum cytokine concentrations in HNSCC patients in order to detect any changes in IL-10, IL-12 and IL-18, compared with non-tumour controls. The relationship between cytokine levels and standard clinicopathological features, including tumour site, tumour stage and presence of nodal metastasis, was also examined. Fifty-seven patients with primary HNSCC were prospectively recruited, together with 40 non-tumour control patients with a similar age and sex distribution. Serum cytokine levels were measured using commercial quantitative enzyme-linked immunosorbent assay. The HNSCC patients had significantly lower IL-12 levels (median; interquartile range) than controls (42.8 pg/ml, 26.2-61.6 vs 52.3 pg/ml, 37.5-113.7; p=0.018). Also, patients were more likely to have detectable IL-10 levels than were controls, as IL-10 was positive in 27/55 patients but in only 9/39 controls (p=0.011). Furthermore, IL-10 detectability varied according to primary site, being more commonly observed in hypopharyngeal and laryngeal tumours, and IL-10 was more likely to be detected with advanced tumour stage (T3 and T4). No differences in IL-18 levels were observed between patients and controls (p=0.169). These results suggest (in agreement with studies on other solid malignancies) that HNSCC causes a significant change in the serum levels of specific Th1 and Th2 cytokines, producing an in vivo environment that is unlikely to promote an effective cell-mediated anti-tumour response.

Adult↗

Carriage of group B streptococcus in pregnant women from Oxford, UK.

OBJECTIVE: To investigate asymptomatic vagino-rectal carriage of group B streptococcus (GBS) in pregnant women. METHODS: Women in the final trimester of pregnancy were recruited. A single vagino-rectal swab was taken, with consent, for culture of GBS. Two microbiological methods for isolation of GBS from vagino-rectal swabs were compared. The distribution of capsular serotypes of the GBS identified was determined. Epidemiological data for a subset (n = 167) of the pregnant women participating were examined. RESULTS: 21.3% were colonised vagino-rectally with GBS. Risk factors for neonatal GBS disease (maternal fever, prolonged rupture of membranes, and preterm delivery) were present in 34 of 167 women (20.4%), and the presence of these factors correlated poorly with GBS carriage. Capsular serotypes III (26.4%), IA (25.8%), V (18.9%), and IB (15.7%) were prevalent in the GBS isolates. Selective broth culture of vagino-rectal swabs was superior to selective plate culture, but the combination of both methods was associated with increased detection of GBS (7.5%). An algorithm for the identification of GBS from vagino-rectal swabs was developed. CONCLUSIONS: GBS carriage is prevalent in pregnant women in Oxfordshire, UK. The poor correlation between risk factors and GBS carriage requires further investigation in larger groups, given that the identification of these surrogate markers is recommended to guide administration of intrapartum antibiotic prophylaxis by the Royal College of Obstetricians of the UK. A selective broth culture detected more GBS carriers than a selective plate culture.

Algorithms↗

The genome of the social amoeba Dictyostelium discoideum.

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

ATP-Binding Cassette Transporters↗

DNA sequence and analysis of human chromosome 9.

Chromosome 9 is highly structurally polymorphic. It contains the largest autosomal block of heterochromatin, which is heteromorphic in 6-8% of humans, whereas pericentric inversions occur in more than 1% of the population. The finished euchromatic sequence of chromosome 9 comprises 109,044,351 base pairs and represents >99.6% of the region. Analysis of the sequence reveals many intra- and interchromosomal duplications, including segmental duplications adjacent to both the centromere and the large heterochromatic block. We have annotated 1,149 genes, including genes implicated in male-to-female sex reversal, cancer and neurodegenerative disease, and 426 pseudogenes. The chromosome contains the largest interferon gene cluster in the human genome. There is also a region of exceptionally high gene and G + C content including genes paralogous to those in the major histocompatibility complex. We have also detected recently duplicated genes that exhibit different rates of sequence divergence, presumably reflecting natural selection.

Base Composition↗

The DNA sequence and analysis of human chromosome 13.

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.

Chromosome Mapping↗

Medical needs of people with intellectual disability require regular reassessment, and the provision of client- and carer-held reports.

BACKGROUND: Previous work has indicated a wide range of unmet medical health needs in people with intellectual disability (ID). METHODS: A profile of recorded medical needs was produced for 589 people with ID through a detailed search of individual medical and nursing case records. Specialist optometric and audiological assessments were offered, and reports were provided in technical and plain English terms. A Health Watch project delivered folders with copies of the plain English reports to 60 individuals and carers. RESULTS: The case record review indicated a wide range of medical disorders; however, exact diagnoses and counselling regarding underlying neurological conditions were seldom recorded. Assessed levels of hearing and vision loss were much greater than had been previously recognized. The Health Watch reports were welcomed by the clients and carers. CONCLUSIONS: If satisfactory healthcare is to be achieved for people with ID, medical needs must be monitored, regular specialist reassessments offered, access to specialist services facilitated and reports clearly explained to carers.

Adolescent↗

Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.

Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.

Animals↗

Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2).

Streptomyces coelicolor is a representative of the group of soil-dwelling, filamentous bacteria responsible for producing most natural antibiotics used in human and veterinary medicine. Here we report the 8,667,507 base pair linear chromosome of this organism, containing the largest number of genes so far discovered in a bacterium. The 7,825 predicted genes include more than 20 clusters coding for known or predicted secondary metabolites. The genome contains an unprecedented proportion of regulatory genes, predominantly those likely to be involved in responses to external stimuli and stresses, and many duplicated gene sets that may represent 'tissue-specific' isoforms operating in different phases of colonial development, a unique situation for a bacterium. An ancient synteny was revealed between the central 'core' of the chromosome and the whole chromosome of pathogens Mycobacterium tuberculosis and Corynebacterium diphtheriae. The genome sequence will greatly increase our understanding of microbial life in the soil as well as aiding the generation of new drug candidates by genetic engineering.

Bacterial Proteins↗

The genome sequence of Schizosaccharomyces pombe.

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.

Base Sequence↗

A superfamily of variant genes encoded in the subtelomeric region of Plasmodium vivax.

The malarial parasite Plasmodium vivax causes disease in humans, including chronic infections and recurrent relapses, but the course of infection is rarely fatal, unlike that caused by Plasmodium falciparum. To investigate differences in pathogenicity between P. vivax and P. falciparum, we have compared the subtelomeric domains in the DNA of these parasites. In P. falciparum, subtelomeric domains are conserved and contain ordered arrays of members of multigene families, such as var, rif and stevor, encoding virulence determinants of cytoadhesion and antigenic variation. Here we identify, through the analysis of a continuous 155,711-base-pair sequence of a P. vivax chromosome end, a multigene family called vir, which is specific to P. vivax. The vir genes are present at about 600-1,000 copies per haploid genome and encode proteins that are immunovariant in natural infections, indicating that they may have a functional role in establishing chronic infection through antigenic variation.

Adult↗

Massive gene decay in the leprosy bacillus.

Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits.

Animals↗

Effects of social support and education on health care costs for patients with fibromyalgia.

OBJECTIVE: The rising costs of health care are of great concern, particularly for the chronically ill. Interventions that promote health status and well being while teaching appropriate use of the health care system have led to cost savings among patients with osteoarthritis. We carried out social support and education interventions with patients with fibromyalgia (FM) and assessed the effect on health care costs, psychosocial variables, and health status. METHODS: Participants were 600 patients with FM who were members of a health maintenance organization. They were randomly assigned to one of 2 experimental groups (social support; social support and education) or to a no-treatment control group. Assessments were conducted at baseline and following a one year intervention. Health care cost data were obtained directly from participants' medical records. RESULTS: Results indicated significant reductions in all groups' costs of prescriptions, laboratory tests, and visits to a nurse, nurse practitioner and/or physicians' assistant. All groups also showed improvements on variables assessing effect of FM, self-efficacy, depression, and knowledge of FM. The social support and education group was less helpless after one year than the other groups; differential changes for all other variables were not significant. CONCLUSION: The study did not reveal differential changes in health care costs among participants in the experimental and control groups. These findings emphasize the importance of using objective health care utilization data when calculating health care costs, as well as the value of including a no-treatment control group to prevent erroneous conclusions about treatment efficacy.

Female↗

Prevalence of small inversions in yeast gene order evolution.

Gene order evolution in two eukaryotes was studied by comparing the Saccharomyces cerevisiae genome sequence to extensive new data from whole-genome shotgun and cosmid sequencing of Candida albicans. Gene order is substantially different between these two yeasts, with only 9% of gene pairs that are adjacent in one species being conserved as adjacent in the other. Inversion of small segments of DNA, less than 10 genes long, has been a major cause of rearrangement, which means that even where a pair of genes has been conserved as adjacent, the transcriptional orientations of the two genes relative to one another are often different. We estimate that about 1,100 single-gene inversions have occurred since the divergence between these species. Other genes that are adjacent in one species are in the same neighborhood in the other, but their precise arrangement has been disrupted, probably by multiple successive multigene inversions. We estimate that gene adjacencies have been broken as frequently by local rearrangements as by chromosomal translocations or long-distance transpositions. A bias toward small inversions has been suggested by other studies on animals and plants and may be general among eukaryotes.

Candida albicans↗

Effect of general practitioner hospitals on district general hospital bed use in the Highlands of Scotland.

OBJECTIVE: To examine hospital bed use by General Practices with and without access to General Practitioner beds. DESIGN: Information from the Contract Management System for General Medicine and Surgery, and from SMR returns for Geriatric Medicine and GP beds was used to compare hospital bed use in District General Hospitals (DGHs) and in General Practitioner beds for practices with and without access to GP beds. Age adjusted rates were calculated for overall use of each specialty. SETTING: All General Practices in the Highland Health Board area for December 1995-April 1997. RESULTS: Compared to practices with no access to GP beds, practices with access used 39.4% fewer bed days per 1000 patients for medical specialties; 18% fewer bed days for surgical specialties; 34.5% fewer bed days for geriatric medicine, and 4.9% fewer bed days for other DGH specialties. Taking into account GP bed day use, practices with access to GP beds used 6.1% more hospital bed days per 1000 patients than did practices with no access. CONCLUSION: These findings largely replicate work in England that found substantial decreases in General Medical and Geriatric Medicine bed use in Practices with access to GP beds, combined with an overall increase in occupied bed day use of 6-8% per 1000 patients. The lower use of surgical beds was unexpected, and may reflect more flexible use of GP beds in the Highlands for observation or rehabilitation, possibly related to the far greater distances involved than in the English studies.

Adolescent↗

The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum.

Analysis of Plasmodium falciparum chromosome 3, and comparison with chromosome 2, highlights novel features of chromosome organization and gene structure. The sub-telomeric regions of chromosome 3 show a conserved order of features, including repetitive DNA sequences, members of multigene families involved in pathogenesis and antigenic variation, a number of conserved pseudogenes, and several genes of unknown function. A putative centromere has been identified that has a core region of about 2 kilobases with an extremely high (adenine + thymidine) composition and arrays of tandem repeats. We have predicted 215 protein-coding genes and two transfer RNA genes in the 1,060,106-base-pair chromosome sequence. The predicted protein-coding genes can be divided into three main classes: 52.6% are not spliced, 45.1% have a large exon with short additional 5' or 3' exons, and 2.3% have a multiple exon structure more typical of higher eukaryotes.

Animals↗

Analysis of CD34 populations in mobilised peripheral blood stem cell harvests and in bone marrow by fluorescent in situ hybridisation for the bcr/abl gene fusion in patients with chronic granulocytic leukaemia.

For those patients ineligible for allogeneic bone marrow transplant and who are non-responsive to interferon, autotransplant with peripheral blood stem cells (PBSC) mobilised after intensive chemotherapy, may provide a novel approach to improve prognosis in patients with chronic granulocytic leukaemia. PBSC harvests are assessed for CD34-positive cell numbers, which serve as an indicator of engraftment potential, and are also analysed cytogenetically to ascertain tumour cell contamination. However, a more accurate assessment of PBSC harvest contamination requires investigation of the Philadelphia (Ph) status of the CD34pos population, in which the cells that provide long-term engraftment are contained. In this study, we have analysed these levels in mobilised PBSC and also in bone marrow (BM) harvests, taken several weeks prior to mobilising chemotherapy. Using fluorescent in situ hybridisation for the bcr/abl gene fusion, we have shown that the median number of Ph negative cells in CD34pos isolated populations was 14.95% in BM compared to 79.05% in PBSC harvests and that in all PBSC samples tested, Ph positivity in CD34pos populations was always detectable either by FISH or one round PCR methods. In paired assessments of both PBSC and BM harvests, higher levels of Ph negative CD34pos cells (> or = 14%) isolated from BM harvests, taken prior to intensive chemotherapy, correlated with higher levels of Ph negative CD34pos cells (> or = 78.5%) in PBSC harvests. These data may aid in the selection of patients for whom PBSC harvesting, after mobilisation, is more likely to achieve an autograft product containing predominantly Ph negative CD34pos cells and may exclude those patients for whom the risk, morbidity and expense of stem cell harvesting may have no apparent benefit over a chronic phase BM harvest.

Adult↗

Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence.

Countless millions of people have died from tuberculosis, a chronic infectious disease caused by the tubercle bacillus. The complete genome sequence of the best-characterized strain of Mycobacterium tuberculosis, H37Rv, has been determined and analysed in order to improve our understanding of the biology of this slow-growing pathogen and to help the conception of new prophylactic and therapeutic interventions. The genome comprises 4,411,529 base pairs, contains around 4,000 genes, and has a very high guanine + cytosine content that is reflected in the biased amino-acid content of the proteins. M. tuberculosis differs radically from other bacteria in that a very large portion of its coding capacity is devoted to the production of enzymes involved in lipogenesis and lipolysis, and to two new families of glycine-rich proteins with a repetitive structure that may represent a source of antigenic variation.

Chromosome Mapping↗