Search PubMed⌕ Search

Biomedical subjects

J Dixon

Publications and source records attributed to J Dixon.

At least 73 records · Page 4Linked to original sources
PubMed1998

The effect of oral selenium supplementation on human sperm motility.

OBJECTIVES: To determine whether the decline in selenium intake and selenium status in men in the West of Scotland might be a contributory factor to male subfertility. PATIENTS AND METHODS: Two semen samples were collected from patients attending a subfertility clinic and those patients with samples showing reduced motility were invited to participate in an ethically approved double-blind clinically controlled trial with informed consent. Sixty-nine patients were recruited and received either placebo, selenium alone or selenium plus vitamins A, C and E daily for 3 months. A further semen sample was collected at the end of the trial. Plasma selenium status was determined at the beginning and end of the trial period, as was total sperm density and motility. RESULTS: Plasma selenium concentrations were significantly (P < 0.001) higher in both selenium-treated groups than in controls. No significant effect of treatment on sperm density was recorded. Sperm motility increased in both selenium-treated groups, in contrast to a slight decline in the placebo group, but the difference was not significant. However, as the provision of additional vitamins had no effect on any variable measured it was considered justified to combine the two selenium-treated groups and compare them with the placebo treatment. On this basis, selenium treatment significantly (P < 0.002) increased plasma selenium concentrations and sperm motility (P = 0.023) but sperm density was again unaffected. Five men (11%) achieved paternity in the treatment group, in contrast to none in the placebo group. CONCLUSION: This trial confirms the result of an earlier study, that selenium supplementation in subfertile men with low selenium status can improve sperm motility and the chance of successful conception. However, not all patients responded; 56% showed a positive response to treatment. The low selenium status of patients not supplemented again highlights the inadequate provision of this essential element in the Scottish diet.

Adult↗
PubMed1998

Mutations in the Treacher Collins syndrome gene lead to mislocalization of the nucleolar protein treacle.

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. The TCS gene ( TCOF1 ), which is localized to chromosome 5q32-q33.1, recently has been identified by positional cloning. Analysis of TCOF1 revealed that the majority of TCS mutations result in the creation of a premature termination codon. The function of the predicted protein, treacle, is unknown, although indirect evidence from database analyses suggests that it may function as a shuttling nucleolar phosphoprotein. In the current study, we provide the first direct evidence that treacle is a nucleolar protein. An antibody generated against treacle shows that it localizes to the nucleolus. Fusion proteins tagged to a green fluorescent protein reporter were shown to localize to different compartments of the cell when putative nuclear localization signals were deleted. Parallel experiments using conserved regions of the murine homologue of TCOF1 confirmed these results. Site-directed mutagenesis has been used to recreate mutations observed in individuals with TCS. The resulting truncated proteins are mislocalized within the cell, which further supports the hypothesis that an integral part of treacle's function involves shuttling between the nucleolus and the cytoplasm. TCS is, therefore, the first Mendelian disorder resulting from mutations which lead to aberrant expression of a nucleolar protein.

Animals↗
PubMed1998

Assessment of the reproducibility of clinical coding in routinely collected hospital activity data: a study in two hospitals.

BACKGROUND: The aim of the study was to assess the reproducibility of clinical coding in two National Health Service hospitals within North West Thames region. METHODS: A retrospective audit was carried out, of clinical coding in hospital episode statistics, involving comparison of the codes assigned by local staff with those assigned by members of an external team unaware of the locally assigned codes. Where local and external coders disagreed, the records were reviewed for a third time by a further independent coder. The subjects were a random sample of 1607 non-maternity, non-psychiatric admissions occurring between 1991 and 1993, stratified for year and type of disease (asthma, diabetes, appendicitis, fractured femur and 'general'--a random selection of any diagnoses). The main outcome measures were the levels of exact agreement between local and external teams over codes for main diagnosis and procedure, and the level of approximate agreement (over the first three characters of the ICD-9 code for diagnosis and the letter and first two digits of the OPCS-4 code for procedure). For disagreements, the outcome measure was the level of agreement between the 'third' coder and the local and external coders. RESULTS: For the main diagnosis in the 'general' group at hospital A, internal and external coders agreed exactly in 43 per cent of the admissions examined and agreed 'approximately' in 55 per cent (kappa = 0.54). For hospital B the corresponding figures were 60 per cent and 72 per cent (kappa = 0.72). Approximate agreement was higher for the specific diseases considered, particularly for asthma (A: 86 per cent; B: 91 per cent) and fractured femur (A: 84 per cent; B: 89 per cent). For the main procedure at hospital A, there was exact agreement for 58 per cent and approximate agreement for 70 per cent (kappa = 0.66). For hospital B, the corresponding figures were 76 per cent and 83 per cent (kappa = 0.80). In cases of disagreement over the first three digits of the ICD-9 code for main diagnosis, the third coder disagreed with both local and external coders in 53 per cent at hospital A and 38 per cent at hospital B. Agreement was slightly better for discharges in 1992-1993 than in 1991-1992. CONCLUSIONS: The full clinical codes in NHS hospital episode statistics (HES) data should be treated with caution. The first three characters of ICD-9 codes for diagnoses and the OPCS-4 codes for procedures were more reliable. For some specific conditions such as asthma and fractured femur, reliability of the first three characters is much higher (for example, 86 per cent and 91 per cent for asthma in the two hospitals), but for the full codes can be worse. Secondary diagnoses or comorbidities may be significantly undercoded. A higher level of agreement in 1992-1993 than in 1991-1992 suggests that coding may be improving.

Abstracting and Indexing↗
PubMed1998

Adult supraglottitis: an important cause of airway obstruction.

Supraglottitis in the adult can progress rapidly to complete airway obstruction. Successful management requires a high index of clinical suspicion at initial presentation and anticipation of a fulminant course. All cases should be assessed in a resuscitation area by senior medical staff.

Aged↗
PubMed1997

A new Holliday junction resolving enzyme from Schizosaccharomyces pombe that is homologous to CCE1 from Saccharomyces cerevisiae.

The resolution of Holliday junctions is a critical stage in recombination. We describe the identification and initial biochemical characterisation of a new Holliday junction resolvase from Schizosaccharomyces pombe. Resolvase activity was initially detected in partially purified cell-free extracts of S. pombe. Resolution of X-junction DNA occurred by the introduction of symmetrical cuts in strands of the same polarity. All cuts occurred 3' of thymine nucleotides with a possible preference for cleavage one nucleotide 3' from the point of strand crossover. During the course of these studies, a potential S. pombe homologue of the Saccharomyces cerevisiae Cruciform Cutting Endonuclease I was identified in the database (SpCCE1). The gene was cloned by PCR, overexpressed in Escherichia coli and its product purified as a His-tagged fusion protein. Purified SpCCE1 binds to X-junctions in a structure-specific manner and resolves them to nicked linear duplex products that are repairable by DNA ligase. SpCCE1 cuts X-junctions in precisely the same way as the resolvase activity from partially purified extracts of S. pombe, indicating that they are probably the same. Finally, we show that SpCCE1 can function as a Holliday junction resolvase in vivo by its ability to complement a resolvase-deficient strain of E. coli.

Bacterial Proteins↗
PubMed1997

Funding the NHS. Is the NHS sustainable?

The survival of the NHS lies largely in the hands of government, and this article suggests steps that it should take to deal with pressures on the NHS in terms of funding, managing efficiency, and demands. Changes to the system of funding may be unfeasible, but management could be improved by research to allow greater understanding of the local effects of national policies. Alternatively health authorities could be given more freedom to manage funds, although this would have to be accompanied by stiff sanctions for those who failed. Demand could be contained by strengthening policies to ensure that new technologies are cost effective. The government could try to reduce demands arising from increased expectations by encouraging informed public debate about priorities and influencing the availability of private health care. All these efforts should be guided by the values underpinning the NHS, which should be debated and decided collectively and confirmed in a new charter for NHS's 50th anniversary in 1998.

Demography↗
PubMed1997

Funding the NHS. A little local difficulty?

The media have been full of reports of crisis in the NHS. Although national analyses suggest that the NHS should be able to cope within the increases in spending it has been given, local pressures can leave parts of the service struggling. Firstly, the change to allocation of funds on the basis of population needs has meant that some authorities and trusts have had effective cuts in their budgets, requiring them to trim services. Secondly, the government's insistence on an annual 3% increase in efficiency may have resulted in authorities taking short term measures that actually decrease efficiency in the long term. Thirdly, health authorities have had to bear the costs of national targets such as reducing waiting lists and junior doctors' hours as well as local problems such as higher numbers of mentally disordered offenders. However, all these factors can be controlled by national or local management and so their impact is not inevitable.

Efficiency↗
PubMed1997

Can the NHS cope in future?

Four potential pressures are likely to determine whether the NHS will be able to cope in future: the change in population structure, changes in level of morbidity, introduction of new technologies, and increasing expectations of patients and NHS providers. New technology and changes in expectations are likely to have the biggest effect and are also the most difficult to quantify. Nevertheless, these pressures are to some extent amenable to control. If the growth in funding continues as it has in the past there is no convincing evidence that the NHS will not continue to cope.

Attitude of Health Personnel↗
PubMed1997

Funding the NHS. Is the NHS underfunded?

Since 1948 there has been constant debate over whether the NHS is underfunded. The debate heats up when crises in the NHS hit the headlines as occurred last year. Various groups, of all shades of the political spectrum, have argued that the NHS is unsustainable with current funding increases because of demands from demographic change, new technology, and increasing expectations. The government is almost a lone voice in arguing that the NHS is sustainable but may not be doing enough to ensure that it remains so in future. This article examines seven broad approaches used to support the case that the NHS is underfunded and concludes that all have flaws. There is no satisfactory answer to the question of whether the NHS is underfunded because the answer requires value judgments that will inevitably give rise to disagreements.

Attitude to Health↗
PubMed1997

Atelosteogenesis syndromes: a review, with comments on their pathogenesis.

The clinical, radiographic, and morphological findings in 25 cases of atelosteogenesis and boomerang dysplasia have been reviewed. The review confirms the nosologic grouping of atelosteogenesis type I with boomerang dysplasia and the clinical and radiographic overlap of features between atel- osteogenesis I and atelosteogene- sis II (synonymous with De la Chapelle dysplasia) and a group of patients with atelosteogenesis type III. A common pathogenesis is suggested for atelosteogenesis type I and boomerang dysplasia. A marked excess of male fetuses with boomerang dysplasia was observed. Atelosteogenesis type II shows distinctive chondro-osseous histopathology with a major disturbance in cartilage matrix macromolecules. An overlap of phenotypic, radiographic, morphological, and cartilage histochemical features with those observed in diastrophic dysplasia and achondrogenesis type IB suggests that atelosteogenesis type II has common pathogenetic features with disorders of sulfation of connective tissue matrix macro- molecules.

Bone Diseases, Developmental↗
PubMed1997

Tumors around implants.

In 1989, A. G. Apley recommended cautious surveillance of malignant tumors that developed in association with orthopaedic implants. This retrospective review of the Bristol Bone Tumour Register between 1980 and 1992 reports on 240 malignant soft tissue sarcomas. Eighteen developed in the thigh region of patients more than 50 years old, and 4 of these developed in the soft tissues around a hip arthroplasty.

Aged↗
PubMed1997

Sequence analysis, identification of evolutionary conserved motifs and expression analysis of murine tcof1 provide further evidence for a potential function for the gene and its human homologue, TCOF1.

The gene mutated in Treacher Collins syndrome, an autosomal dominant disorder of facial development, has recently been cloned. While the function of the predicted protein, Treacle, is unknown, it has been shown to share a number of features with the highly phosphorylated nucleolar phosphoproteins, which play a role in nucleolar-cytoplasmic transport. In the current study, the murine homologue of the Treacher Collins syndrome gene has been isolated and shown to encode a low complexity, serine/alanine-rich protein of 133 kDa. Interspecies comparison indicates that the proteins display 61.5% identity, with the level of conservation being greatest in the regions of acidic/basic amino acid repeats and nuclear localization signals. These features are shared with the nucleolar phosphoproteins. Confirmation that the gene isolated in the current study is orthologous with the Treacher Collins syndrome gene was provided by the demonstration that it mapped to central mouse chromosome 18 in a conserved syntenic region with human chromosome 5q21-q33. Expression analysis in the mouse indicated that the gene was expressed in a wide variety of embryonic and adult tissues. Peak levels of expression in the developing embryo were observed at the edges of the neural folds immediately prior to fusion, and also in the developing branchial arches at the times of critical morphogenetic events. These observations support a role for the gene in the development of the craniofacial complex and provide further evidence that the gene encodes a protein which may be involved in nucleolar-cytoplasmic transport.

Amino Acid Sequence↗
PubMed1997

Identification of the complete coding sequence and genomic organization of the Treacher Collins syndrome gene.

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. Recently, the demonstration of a series of 10 mutations within a partial-length cDNA clone have indicated that the TCS gene (TCOF1) has been positionally cloned. Although it has been shown that the gene is expressed in a wide variety of fetal and adult tissues, database sequence comparisons have failed to provide significant information on the function of the gene. In the current investigation, a combination of cDNA library screening and rapid amplification of cDNA ends has permitted the isolation of the complete coding sequence of TCOF1, which is encoded by 26 exons and predicts a low complexity, serine/alanine-rich protein of approximately 144 kD. The use of a variety of bioinformatics tools has resulted in the identification of repeated units within the gene, each of which maps onto an individual exon. The predicted protein Treacle contains numerous potential phosphorylaiton sites, a number of which map to similar positions within the repeated units, and shows weak but significant homology to the nucleolar phosphoproteins. Although the precise function of Treacle remains unknown, these observations suggest that phosphorylation may be important for its role in early embryonic development and that it may play a role in nucleolar-cytoplasmic shuttling. The information presented in this study will allow continued mutation analysis in families with a history of TCS and should facilitate continued experimentation to shed further light on the function of the gene/protein during development of the craniofacial complex.

Amino Acid Sequence↗