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Biomedical subjects

R Kingston

Publications and source records attributed to R Kingston.

At least 19 recordsLinked to original sources
PubMed2002

Antibiotic prophylaxis for dental or urological procedures following hip or knee replacement.

OBJECTIVES: Reports of prosthetic joint infection associated with urological or dental procedures have prompted suggestions that these patients require antibiotic prophylaxis, but no guidelines have been agreed. We have polled orthopaedic surgeons, urologists, and dentists on this issue. METHODS: The questions asked were: could infection of a joint prosthesis result from a dental or urological procedure; does the risk of infection warrant patients informing their dentist or urologist about their joint replacement; should these patients have prophylactic antibiotics for (a) routine procedures and (b) lengthy procedures. RESULTS: Urologists and orthopaedic surgeons agreed that infection could probably result from urological procedures and that patients should definitely inform their urologist about their prosthesis. Orthopaedic surgeons thought that antibiotics were definitely indicated for routine and lengthy urological procedures while urologists thought antibiotics were probably indicated. Orthopaedic surgeons thought that infection probably could result from dental procedures, while dentists answered "don't know". Both groups agreed that patients should definitely inform their dentist about their prosthesis. Orthopaedic surgeons thought that antibiotics probably were necessary for routine and lengthy dental procedures, whereas dentists answered "probably not" and "don't know", respectively. CONCLUSIONS: These results could provide the basis for a consensus regarding prophylactic antibiotic use in this growing patient population.

Anti-Bacterial Agents↗
PubMed2001

Rvb1p and Rvb2p are essential components of a chromatin remodeling complex that regulates transcription of over 5% of yeast genes.

Eukaryotic Rvb1p and Rvb2p are two highly conserved proteins related to the helicase subset of the AAA+ family of ATPases. Conditional mutants in both genes show rapid changes in the transcription of over 5% of yeast genes, with a similar number of genes being repressed and activated. Both Rvb1p and Rvb2p are required for maintaining the induced state of many inducible promoters. ATP binding and hydrolysis by Rvb1p and Rvb2p is individually essential in vivo, and the two proteins are associated with each other in a high molecular weight complex that shows ATP-dependent chromatin remodeling activity in vitro. Our findings show that Rvb1p and Rvb2p are essential components of a chromatin remodeling complex and determine genes regulated by the complex.

Adenosine Triphosphatases↗
PubMed2001

Treatment of surgical patients is evidence-based.

OBJECTIVES: To assess the type of evidence that supported our management of surgical patients. DESIGN: Retrospective audit. SETTING: Teaching hospital, Republic of Ireland. PATIENTS: All 222 patients admitted by two surgical teams during one month. Patients admitted for diagnostic procedures were included if they were treated as a result. MAIN OUTCOME MEASURES: Diagnosis and treatment were established from the notes. Evidence for each intervention was then sought in MEDLINE 1986-1999, Best Evidence 1991-1999, and the Cochrane Database of Systematic Reviews Issue 3, 1999, and graded into one of five categories: systematic review, meta-analysis, randomised controlled trial, prospective study, or retrospective study. RESULTS: Treatment was supported by systematic review in 14, by meta-analysis in 12, by randomised controlled trial in 75, by prospective studies in 55, by retrospective studies in 58, and by no evidence in 8. CONCLUSIONS: Everyday surgical practice in our unit is supported by good quality evidence from recent publications.

Adolescent↗
PubMed2001

How informed is consent? Use of an information booklet in patients undergoing total hip replacement.

For informed consent, patients must understand the risks and benefits of the proposed procedure. Fifty patients undergoing total hip replacement (THR) participated in an evaluation of a newly devised information booklet. Patients' understanding of the risks and benefits of THR was assessed using a questionnaire before and after they had read the booklet. Pre-booklet patients knew on average 2 benefits of THR, compared with 3 afterwards. Twenty-two patients initially identified no alternative treatment to THR. Those who knew an alternative stated on average 1 treatment compared with 2 in the post-booklet group. Fifteen patients identified no risks of THR initially, compared with two after reading the booklet. Initially patients reported 1 risk, versus 3 after reading the booklet. Forty-eight patients thought that the booklet increased their understanding of THR and its risks. Fourteen found it upsetting, but acceptable. Forty-six patients wished to keep the booklet.

Arthroplasty, Replacement, Hip↗
PubMed2000

Generation of superhelical torsion by ATP-dependent chromatin remodeling activities.

ATP-dependent chromatin remodeling activities participate in the alteration of chromatin structure during gene regulation. All have DNA- or chromatin-stimulated ATPase activity and many can alter the structure of chromatin; however, the means by which they do this have remained unclear. Here we describe a novel activity for ATP-dependent chromatin remodeling activities, the ability to generate unconstrained negative superhelical torsion in DNA and chromatin. We find that the ability to distort DNA is shared by the yeast SWI/SNF complex, Xenopus Mi-2 complex, recombinant ISWI, and recombinant BRG1, suggesting that the generation of superhelical torsion represents a primary biomechanical activity shared by all Snf2p-related ATPase motors. The generation of superhelical torque provides a potent means by which ATP-dependent chromatin remodeling activities can manipulate chromatin structure.

Adenosine Triphosphate↗
PubMed2000

BRG-1 is recruited to estrogen-responsive promoters and cooperates with factors involved in histone acetylation.

Several factors that mediate activation by nuclear receptors also modify the chemical and structural composition of chromatin. Prominent in this diverse group is the steroid receptor coactivator 1 (SRC-1) family, which interact with agonist-bound nuclear receptors, thereby coupling them to multifunctional transcriptional coregulators such as CREB-binding protein (CBP), p300, and PCAF, all of which have potent histone acetyltransferase activity. Additionally factors including the Brahma-related gene 1 (BRG-1) that are involved in the structural remodeling of chromatin also mediate hormone-dependent transcriptional activation by nuclear receptors. Here, we provide evidence that these two distinct mechanisms of coactivation may operate in a collaborative manner. We demonstrate that transcriptional activation by the estrogen receptor (ER) requires functional BRG-1 and that the coactivation of estrogen signaling by either SRC-1 or CBP is BRG-1 dependent. We find that in response to estrogen, ER recruits BRG-1, thereby targeting BRG-1 to the promoters of estrogen-responsive genes in a manner that occurs simultaneous to histone acetylation. Finally, we demonstrate that BRG-1-mediated coactivation of ER signaling is regulated by the state of histone acetylation within a cell. Inhibition of histone deacetylation by trichostatin A dramatically increases BRG-1-mediated coactivation of ER signaling, and this increase is reversed by overexpression of histone deacetylase 1. These studies support a critical role for BRG-1 in ER action in which estrogen stimulates an ER-BRG-1 association coupling BRG-1 to regions of chromatin at the sites of estrogen-responsive promoters and promotes the activity of other recruited factors that alter the acetylation state of chromatin.

Acetylation↗
PubMed1999

Ikaros DNA-binding proteins direct formation of chromatin remodeling complexes in lymphocytes.

The Ikaros gene family encodes zinc finger DNA-binding proteins essential for lineage determination and control of proliferation in the lymphoid system. Here, we report that, in the nucleus of a T cell, a major fraction of Ikaros and Aiolos proteins associate with the DNA-dependent ATPase Mi-2 and histone deacetylases, in a 2 MD complex. This Ikaros-NURD complex is active in chromatin remodeling and histone deacetylation. Upon T cell activation, Ikaros recruits Mi-2/HDAC to regions of heterochromatin. These studies reveal that Ikaros proteins are capable of targeting chromatin remodeling and deacetylation complexes in vivo. We propose that the restructuring of chromatin is a key aspect of Ikaros function in lymphocyte differentiation.

Adenosine Triphosphatases↗
PubMed1999

Physical and psychological needs of patients dying from colo-rectal cancer.

Sixty-one patients suffering from terminal colo-rectal cancer were interviewed in depth by trained research nurses. The nurses used a semistructured interview, a concerns checklist and the Psychiatric Assessment Schedule to determine patients' key physical complaints, their main concerns and whether or not an affective disorder was present. The interviewers' estimates of these aspects were then compared with the assessments of 48 carers and 58 general practitioners (GPs). The congruence between patients' and carers' reports was reasonable for appetite loss (77%), nausea and vomiting (75%) and pain (72%), and the rate of false positive reporting was low. However, there was much less congruence for breathlessness (48%) and pyrexia (32%). There was even less congruence between the estimates of patients' physical symptoms and GPs' perceptions. The highest congruence was for pain (42%). The congruence was low for appetite loss (8%) and breathlessness (5%). The congruence between patients' and carers' perceptions of the patients' major concerns was low, being at best 33% for patients' concerns about their physical illness. The rate of false positive reporting by carers was high. The carers' major concerns included the patients' illness (47%), the future (33%) and the emotional demands being put on them (23%). Thirteen (22%) of the 59 patients completing a full interview were suffering from an affective disorder. This had been recognized by the GP in only five cases and six patients who had a normal mood were wrongly diagnosed as being depressed. Of the carers interviewed, 22 (46%) considered symptom control had been inadequate and 23 (48%) felt they had no relief from the burden of caring or had too little help. Sixteen (33%) had recently suffered from a major depressive illness, generalized anxiety disorder or adjustment disorder. It is concluded that it is unreliable to rely on carers' proxy reports of the symptoms experienced by terminally ill patients; more accurate personal assessments are needed where possible. It is likely that this will only be achieved by ensuring that those health professionals involved in palliative care have training in the relevant assessment skills.

Aged↗
PubMed1998

Direct mass spectrometric peptide profiling and sequencing of single neurons reveals differential peptide patterns in a small neuronal network.

Mass spectrometry (MS) was employed to detect and structurally characterize peptides in two functionally related neurons, named VD1 and RPD2, which form a network involved in the modulation of heartbeat in Lymnaea. Matrix-assisted laser desorption/ionization MS, directly applied to single neurons VD1 and RPD2, showed overlapping yet distinct mass profiles, with a subset of putative peptides specifically present in neuron VD1. Direct tandem MS of a single VD1 neuron revealed the primary structures of the VD1-specific peptides, which were identified as members of the family of small cardioactive peptides. Based on the tandem MS data, a degenerate oligonucleotide was made for use in a polymerase chain reaction strategy to isolate the cDNA encoding the precursor to the small cardioactive peptides from a brain-specific cDNA library. The calculated masses of the mature, posttranslationally modified peptides, as predicted from the corresponding cDNA, agreed with the measured masses of the actual peptides, as detected in single-cell MS analysis. In situ hybridization studies showed that the transcript encoding the precursor is present in VD1, but not in RPD2, thus corroborating the single-cell MS analysis. Finally, the small cardioactive peptides were shown to enhance the contractions of the auricle in vitro.

Amino Acid Sequence↗
PubMed1997

Immune responses, not promoter inactivation, are responsible for decreased long-term expression following plasmid gene transfer into skeletal muscle.

Long-term high-level in vivo gene expression appears to depend on the promoter chosen to drive the gene of choice. In many cases the promoter appears to 'switch off' some time after in vivo gene transfer. We demonstrate that, following intramuscular injection of beta-galactosidase reporter plasmids, promoter 'switch off' is due to elimination of fibres expressing the transferred reporter gene by activation of a Th1 (cytotoxic) immune response. This finding, in the absence of stimulation of the immune system by viral vector proteins, has implications not only for gene transfer experiments but for the future of muscle-directed gene therapy.

Animals↗
PubMed1997

Incidence of hereditary non-polyposis colorectal cancer in a population-based study of 1137 consecutive cases of colorectal cancer.

BACKGROUND: Previous reports have indicated that 5-13 per cent of colorectal cancer is hereditary. However, the proportion of cases arising as a result of mutations in the hereditary non-polyposis colorectal cancer (HNPCC) genes remains to be determined. METHODS: This study is a part prospective, part retrospective review of all cases of colorectal cancer from a district hospital over 14 years. Some 1137 consecutive patients with colorectal cancer were questioned about their family history of cancer and details were logged on a database. For the past 4 years each case has been re-evaluated where possible. RESULTS: Some 118 patients indicated initially that they had a first-degree relative with colorectal cancer, but on re-evaluation there were significant discrepancies. Only three cases (0.3 per cent) occurred in families which strictly fulfilled the criteria for HNPCC and there were no cases of familial adenomatous polyposis. A total of 16 patients (1.4 per cent) fulfilled looser criteria for HNPCC. CONCLUSION: This population-based study has shown a lower frequency of familial bowel cancer than previous studies and may reflect a lower incidence of inherited mutations in the HNPCC DNA mismatch repair genes than is currently accepted.

Adult↗
PubMed1995

An improved method for clenbuterol screening using high resolution selected ion recording.

A method has been developed using reliable GC derivatization techniques interfaced with a high resolution mass spectrometer. The method has proved successful for the detection of low levels (less than 1 ppm) of clenbuterol in complex biological matrices. Selected ion recording of two characteristic isotopic fragment ions provides a specific mode of detection by verifying the GC retention time of these ions and also by comparing their relative abundance. Analysis of urine samples demands higher mass spectrometric resolution, and 40 000 (10% valley) was found to be a prerequisite for accurate integration of the drug-related chromatographic peaks. The method developed is suitable for adaptation to a completely unattended automated routine incorporating sample injection, storage and retrieval of source tuning parameters, and data processing.

Adrenergic beta-Agonists↗
PubMed1995

Monoclonal antibodies identifying chick gonadal cells.

1. The aim of the present study was to raise monoclonal antibodies (MAbs) which discriminate gonadal cell types in chickens. 2. A panel of 180 MAbs was generated, from which 14 were chosen for their specificity. 3. These MAbs were characterised immunohistologically on frozen sections of embryonic, newly-hatched and adult, male and female, left gonads. 4. Three of these MAbs are described: AGC5, AGC7, and AGC13 which recognise respectively germinal epithelial cells, supporting cells and germ cells. 5. These MAbs may be useful in following the developmental pathways in the chicken gonad and analysing the interactive role(s) taking place between gonadal stromal cells and primordial germ cells.

Aging↗