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Biomedical subjects

D Hodgson

Publications and source records attributed to D Hodgson.

At least 19 recordsLinked to original sources
PubMed2007

An update on localised prostate cancer.

Prostate cancer remains a most intriguing condition, which poses unique challenges. On reviewing recent literature on localised disease (confined within the capsule T1 or T2, N0, M0), it would seem that it is over treated, resulting in significant morbidity. We now have strong evidence, however, that there can be mortality associated with 'watchful waiting'. Clinicians should, therefore, aim to identify men at risk of progression in order that they should be treated effectively with minimal adverse effects. In this paper, we report on recent developments in the expanding array of management options available.

Cohort Studies↗
PubMed2001

Signaling in channel/enzyme multimers: ATPase transitions in SUR module gate ATP-sensitive K+ conductance.

ATP-sensitive potassium (K(ATP)) channels are bifunctional multimers assembled by an ion conductor and a sulfonylurea receptor (SUR) ATPase. Sensitive to ATP/ADP, K(ATP) channels are vital metabolic sensors. However, channel regulation by competitive ATP/ADP binding would require oscillations in intracellular nucleotides incompatible with cell survival. We found that channel behavior is determined by the ATPase-driven engagement of SUR into discrete conformations. Capture of the SUR catalytic cycle in prehydrolytic states facilitated pore closure, while recruitment of posthydrolytic intermediates translated in pore opening. In the cell, channel openers stabilized posthydrolytic states promoting K(ATP) channel activation. Nucleotide exchange between intrinsic ATPase and ATP/ADP-scavenging systems defined the lifetimes of specific SUR conformations gating K(ATP) channels. Signal transduction through the catalytic module provides a paradigm for channel/enzyme operation and integrates membrane excitability with metabolic cascades.

ATP-Binding Cassette Transporters↗
PubMed2001

Adenylate kinase phosphotransfer communicates cellular energetic signals to ATP-sensitive potassium channels.

Transduction of energetic signals into membrane electrical events governs vital cellular functions, ranging from hormone secretion and cytoprotection to appetite control and hair growth. Central to the regulation of such diverse cellular processes are the metabolism sensing ATP-sensitive K+ (K(ATP)) channels. However, the mechanism that communicates metabolic signals and integrates cellular energetics with K(ATP) channel-dependent membrane excitability remains elusive. Here, we identify that the response of K(ATP) channels to metabolic challenge is regulated by adenylate kinase phosphotransfer. Adenylate kinase associates with the K(ATP) channel complex, anchoring cellular phosphotransfer networks and facilitating delivery of mitochondrial signals to the membrane environment. Deletion of the adenylate kinase gene compromised nucleotide exchange at the channel site and impeded communication between mitochondria and K(ATP) channels, rendering cellular metabolic sensing defective. Assigning a signal processing role to adenylate kinase identifies a phosphorelay mechanism essential for efficient coupling of cellular energetics with K(ATP) channels and associated functions.

Adenosine Diphosphate↗
PubMed2001

Outcomes of submandibular duct re-implantation for sialorrhoea.

Drooling is an important factor affecting the quality of lives of neurologically impaired children, and surgery often has to be performed. Submandibular duct relocation is a relatively simple procedure with a low complication rate, and has been carried out on 37 patients at the Sheffield Children's Hospital between 1986 and 1998. To determine the short-term and long-term outcome of this procedure, a questionnaire was sent to the parents/wards of the patients. Feedback was also obtained on complications, parents'/carers' perceptions and main concerns about the operation, particularly in those cases which did not improve. Both short-term (82.4%) and long-term (76.5%) control rates were high, and there were few complications, none of which had any long-term adverse effects. The most significant area of parental/carer dissatisfaction and concern in 'failed' cases was 'pain', and it was felt that proper preoperative counselling about analgesia and chances of failure is very important. We conclude that this is a safe, highly successful procedure which significantly improves the quality of lives of the majority of drooling children.

Adolescent↗
PubMed2001

The effect of three different doses of sodium pentosan polysulphate on haematological and haemostatic variables in adult horses.

OBJECTIVE: To evaluate the effects of three different doses of sodium pentosan polysulphate (PPS) on haematological and haemostatic variables in adult horses. DESIGN: Eight adult standardbred horses were used. All horses received a single injection of 0, 3, 6, and 10 mg/kg of PPS at the beginning of each treatment week for 4 weeks so that by the end of the study all horses had received all four doses of PPS. Blood samples were collected at 0, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 168 h after each weekly injection of PPS. Variables measured were packed cell volume, haemoglobin, red blood cell count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, platelet count, white cell count, neutrophil count, lymphocyte count, eosinophil count, monocyte count, serum protein, fibrinogen, prothrombin time, and activated partial thromboplastin time (PTT). Data were analysed using an ANOVA. Significance was set at P < 0.05. RESULTS: There was a dose-dependent increase in PTT. A significant increase in PTT occurrred in all treatment groups when compared to horses receiving 0 mg/kg in which there was no change over time. The PTT values all returned to baseline by 48 h after treatment. The mean neutrophil count was higher 3 h after treatment when compared to time 0. Horses receiving 3 mg/kg of PPS had a higher lymphocyte count 4 h after injection, and those receiving 6 and 10 mg/kg had higher counts at 3,4,6 and 8 h after injection when compared to time 0. At 8 h after injection horses receiving 6 and 10 mg PPS had higher lymphocyte counts than horses not receiving PPS. CONCLUSIONS: PPS causes a dose-dependent prolongation of PTT in horses. At the dose rates currently recommended for treatment of joint problems in horses this increase was small and remained elevated from baseline for up to 24 h. Based on these findings doses of PPS up to 3 mg/kg should not be administered to horses within 24 h of high stress activities or where physical injury may occur.

Animals↗
PubMed2000

A competency-based tool for education.

Through a multidisciplinary team approach, a competency-based tool has been developed to help to assess and identify training and development needs for staff working within the cancer field. The tool assists both individuals and organisations to gain a micro and macro picture of staff's existing skills and their development needs.

Clinical Competence↗
PubMed2000

A cultural change in cancer education and training.

Collaborative education and training is the only way forward for the cancer care work force. The Calman-Hine report has become the benchmark on which to build practice since its launch in 1995. A forward looking group--the Cancer Care Alliance of Teesside, South Durham and North Yorkshire Education Group and the University of Teesside--adopted its principles from the Calman-Hine Report and developed some strategic projects to address and achieve them. A needs assessment of cancer education influenced the agenda within the Cancer Care Alliance. The education portfolio that was developed had a multiprofessional focus, incorporating both academic and non-academic study.

Attitude of Health Personnel↗
PubMed1999

Paediatric epiglottitis: the influence of the Haemophilus influenzae b vaccine, a ten-year review in the Sheffield region.

Cases of acute epiglottitis in children have become very uncommon in recent years. This study set out to find whether the introduction of the Haemophilus influenzae b (Hib) vaccine in the UK in October 1992 has influenced the incidence of acute epiglottitis in the Sheffield region, and whether the pathogenesis has altered. A 10-year retrospective case note review was undertaken. A total of 30 children were treated for acute epiglottitis in Sheffield Children's Hospital over that time period. A sharp decline in the number of cases was found after the vaccine was introduced. Most children presenting with the disease after October 1992 had not been vaccinated. In addition, the pathogens isolated in those children who had received the vaccine were all Streptococci. This is the first study in the UK to examine the influence of the Hib vaccine on acute paediatric epiglottitis.

Catchment Area, Health↗
PubMed1999

Prediction of gene function by genome-scale expression analysis: prostate cancer-associated genes.

We wish to identify genes associated with disease. To do so, we look for novel genes whose expression patterns mimic those of known disease-associated genes, using a method we call Guilt-by-Association (GBA), on the basis of a combinatoric measure of association. Using GBA, we have examined the expression of 40,000 human genes in 522 cDNA libraries, and have discovered several hundred previously unidentified genes associated with cancer, inflammation, steroid-synthesis, insulin-synthesis, neurotransmitter processing, matrix remodeling, and other disease processes. The majority of the genes thus discovered show no sequence similarity to known genes, and thus could not have been identified by homology searches. We present here an example of the discovery of eight genes associated with prostate cancer. Of the 40,000 most-abundant human genes, these 8 are the most closely linked to the known diagnostic genes, and thus are prime targets for pharmaceutical research.

Gene Expression Profiling↗
PubMed1998

Automated sequence preprocessing in a large-scale sequencing environment.

A software system for transforming fragments from four-color fluorescence-based gel electrophoresis experiments into assembled sequence is described. It has been developed for large-scale processing of all trace data, including shotgun and finishing reads, regardless of clone origin. Design considerations are discussed in detail, as are programming implementation and graphic tools. The importance of input validation, record tracking, and use of base quality values is emphasized. Several quality analysis metrics are proposed and applied to sample results from recently sequenced clones. Such quantities prove to be a valuable aid in evaluating modifications of sequencing protocol. The system is in full production use at both the Genome Sequencing Center and the Sanger Centre, for which combined weekly production is approximately 100, 000 sequencing reads per week.

Automation↗
PubMed1997

DNA computing.

DNA computation is a novel and exciting recent development at the interface of computer science and molecular biology. We describe the current activity in this field following the seminal work of Adleman, who recently showed how techniques of molecular biology may be applied to the solution of a computationally intractable problem.

Algorithms↗
PubMed1995

Microwaves for menorrhagia: a new fast technique for endometrial ablation.

Current ablative techniques for treating menorrhagia are unsatisfactory. We tried microwave energy, delivered by an 8 mm diameter probe in the uterine cavity, to treat 23 patients with functional menorrhagia. The mean treatment time was 2 min 12 s (range 50-310 s). 6 months after treatment the success rate is 83%, 13 patients (57%) are amenorrhoeic, and six (26%) are experiencing light menstruation. Three initial failures have been successfully retreated. The technique is safe, and is easier and quicker to perform than current alternatives.

Adult↗
PubMed1994

Measurement of urinary free cortisol by stable isotope dilution mass spectrometry using a new cortisol derivative.

The reaction of the bismethylenedioxy derivative of cortisol (cortisol-BMD) with heptafluorobutyric anhydride to give the corresponding 3,5-dienol heptafluorobutyrate (cortisol-BMD-HFB) has been shown to proceed with dehydration. Acid-promoted dehydration of either cortisol-BMD or cortisol-BMD-HFB, or concurrent dehydration of both, is the proposed reaction mechanism leading to a trienol heptafluorobutyrate, whose chromatographic properties and mass spectral data are consistent with the additional double bond in the C9-C11 position. Forming the 3,5-dienol heptafluorobutyrate of cortisol-BMD in benzene rather than acetone gave a compound whose chromatographic properties and mass spectral data were different to that of the 3,5,9(11)-trienol heptafluorobutyrate but consistent with that of a cortisol-BMD-HFB. The mass fragmentometry of this new cortisol derivative was found to be more suited to the technique of isotope dilution mass spectrometry than the 3,5,9(11)-trienol heptafluorobutyrate, and thus was applied to our intended goal of measuring urinary free cortisol by gas chromatography-mass spectrometry. An efficient and convenient solid-phase extraction technique is employed in our assay to isolate cortisol from 5 ml of urine.

Fluorocarbons↗