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Biomedical subjects

C A Kelly

Publications and source records attributed to C A Kelly.

At least 19 recordsLinked to original sources

Influence of diabetes on peripheral bone mineral density in men: a controlled study.

The aims of the study were to (1) compare peripheral bone mineral density (BMD) in men with diabetes to peripheral BMD in non-diabetic men, and (2) explore factors which may predict BMD in diabetic men. Ninety men with type 2 diabetes and 35 men with type 1 diabetes were randomly selected for participation via a computerised database. Fifty healthy males were also recruited. All patients had peripheral BMD measured by dual energy Xray absorptiometry (DEXA) at the non-dominant distal radius. Information on a number of clinical parameters was obtained by direct questioning, and from patient case notes. The mean age (95% confidence interval (CI)) of the type 1 diabetic group, type 2 diabetic group and control group were, respectively: 49.3 years (44.6-53.9), 62.8 years (60.7-64.8) and 38.5 (34.9-42.1) years. Median (95% CI) Z-scores for the three groups were: -0.18 (-0.68 to +0.32), +0.19 (-0.14 to +0.49) and -0.02 (-0.4 to +0.31), respectively (p=not significant). Only body mass index (BMI) was correlated with BMD in the type 1 diabetic group, and only BMI and age were correlated with BMD in type 2 diabetics. There was no correlation between BMD and glycosylated haemoglobin concentration (HbA(1)c), disease duration or presence of microvascular or macrovascular complications in either of the diabetic groups. We did not find any significant difference in peripheral BMD between patients with type 1 diabetes, type 2 diabetes and controls.

Absorptiometry, Photon↗

Electrocardiogram and cardiovascular changes in thioridazine and chlorpromazine poisoning.

OBJECTIVES: To examine the effects of anti-psychotic medications on cardiovascular parameters in overdose. Specifically, to examine dose-response relationships for thioridazine and chlorpromazine. METHODS: A retrospective study of case records of patients presenting to the Edinburgh poisons treatment unit over 3 years (2000-2002). Information--including that on stated dose ingested, ECG parameters, and pulse and blood pressure--was extracted from case notes. RESULTS: A total of 224 chlorpromazine, 96 thioridazine and 99 patients ingesting other anti-psychotics were evaluated. Full data on all aspects, both dose and cardiovascular change, was available in 96 chlorpromazine, 36 thioridazine and 27 of the other anti-psychotic cases. For thioridazine, there was a significant dose-response relationship for increasing heart rate and increasing QTc but not other cardiovascular changes. For chlorpromazine, there was no dose-response relationship for ECG changes, but there was a significant dose-response relationship for increasing heart rate and reduction in mean blood pressure. CONCLUSIONS: We have confirmed a relationship between increasing dose of thioridazine and prolongation of QTc in overdose patients. No such change was observed with chlorpromazine. Both of these agents are reported to cause QT prolongation, but this study suggests that the nature of these effects is different for each agent. Poisoned patients may offer ways of exploring in more detail, and at a larger dose range, the effects of potentially cardiotoxic drugs in humans.

Adult↗

Are selective serotonin re-uptake inhibitors associated with an increased risk of self-harm by antidepressant overdose?

OBJECTIVE: To investigate likelihood of self-harm by overdose with antidepressant drugs of different types by examining hospital admission data and poisons inquiries and relating them to prescribing. DESIGN: Retrospective analysis of prospectively collected data on overdose admissions, poisons inquiries and prescribing of antidepressants in Edinburgh and Scotland. SETTING: Poisons treatment unit of the Royal Infirmary of Edinburgh and its surrounding catchment for overdose cases and Scotland for poisons inquiries. PARTICIPANTS: All patients admitted to the Royal Infirmary of Edinburgh between 1 January 2000 and 31 December 2002 with an overdose involving an antidepressant. MAIN OUTCOME MEASURES: Overdose admissions (patients) in relation to prescribing in Edinburgh and poisons inquiries in relation to prescription rates in Scotland. RESULTS: There were 1656 admissions involving 1343 patients. The likelihood of admission for an individual patient in relation to volume of prescribing (likelihood ratio: 95%CI) in the catchment was somewhat smaller for amitriptyline (0.83:0.74-0.92) and sertraline (0.79:0.63-0.99), and somewhat greater for mirtazapine (1.99:1.57-2.51), trazadone (1.30:1.09-1.54) and venlafaxine (0.97:1.81-1.16) [corrected] For poisons inquiries in Scotland, the excess for venlafaxine and mirtazapine was confirmed and likelihood of an inquiry lowest for selective serotonin re-uptake inhibitors (SSRIs). CONCLUSIONS: There was no evidence of an excess likelihood of presentation with overdose with SSRIs, and the likelihood was reduced with sertraline. There was a small excess of both admissions and poisons inquiries for mirtazapine and venlafaxine. This is a concern in view of the increased toxicity of venlafaxine in overdose in comparison with SSRIs.

Adult↗

The pattern and significance of abnormal liver function tests in community-acquired pneumonia.

BACKGROUND: The pattern of liver function tests (LFTs) in community-acquired pneumonia has not been investigated in detail. Although abnormal tests are thought to be more frequent in patients with atypical pneumonia, the prognostic value of LFTs have not been clearly established. METHODS: We assessed 96 consecutive patients admitted to one hospital with a chest infection over a period of 6 weeks. The infection was classified as bronchitis or lobar pneumonia on clinical and radiological criteria. The site and severity of the infection were assessed and correlated with LFTs and standard British Thoracic Society prognostic criteria. Mortality and length of stay in survivors were used as major outcome measures. RESULTS: There were 17 deaths (18%) overall and patients with abnormal LFTs were significantly more likely to die than those with normal tests (25% vs. 5%; p=0.026). Length of stay was significantly longer in survivors with abnormal liver function than in those with normal tests (9.7 vs. 5.8 days; p=0.006). A low albumin was the most useful predictor of poor outcome and carried a relative risk of dying of 1.8, comparable to the predictive value of tachypnoea. ALT was increased threefold in those succumbing to their disease, but alkaline phosphatase levels were not predictive of outcome and an increase in gamma GT appeared to be protective. CONCLUSIONS: Abnormal LFTs are common in community-acquired pneumonia and are of prognostic value. Patients with a low albumin or raised ALT are significantly more likely to die from their disease or to stay in hospital for a prolonged period. However, other LFTs are of less value in predicting prognosis.

Journal Article↗

Comparative toxicity of citalopram and the newer antidepressants after overdose.

OBJECTIVE: To compare the toxicity of citalopram, venlafaxine, mirtazapine, and nefazadone after overdose. METHODS: Two-year retrospective review of consecutive patients admitted to the toxicology unit of Edinburgh Royal Infirmary. Outcome measure included physiological variables, ECG recordings, peak creatine kinase, development of arrhythmias, seizure, tremor or agitation, and the need for admission to a critical care facility. RESULTS: A total of 225 patients were studied. Venlafaxine was associated with a significantly higher pulse rate (p < 0.0001) and tremor (p = 0.007) than other antidepressants. Citalopram was associated with a significantly longer QT interval on ECG recording (p < 0.0001) but mean QTc durations were not significantly different between all drugs studied. No arrhythmias were recorded. Only venlafaxine and citalopram caused seizures and were associated with the need for admission to Intensive Care, but there was no significant difference between them. CONCLUSIONS: Mirtazapine and nefazadone appear safe in overdose and were associated with minimal features of neurological or cardiovascular toxicity. Citalopram is more likely to cause QT prolongation but other features of cardiovascular toxicity were uncommon. Both citalopram and venlafaxine are proconvulsants. Venlafaxine also causes more frequent features of the serotonin syndrome.

Administration, Oral↗

Effect of pH on mercury uptake by an aquatic bacterium: implications for Hg cycling.

We studied the effect of increasing hydrogen ion (H+) concentration on the uptake of mercury (Hg(II)) by an aquatic bacterium. Even small changes in pH (7.3-6.3) resulted in large increases in Hg(II) uptake, in defined media. The increased rate of bioaccumulation was directly proportional to the concentration of H+ and could not be explained by assuming that the source of Hg to the bacteria was diffusion of neutrally charged species such as HgCl2. Thus, pH appeared to affect a facilitated mechanism by which Hg(II) is taken up by the cells. Lowering the pH of Hg solutions mixed together with natural dissolved organic carbon, or with whole lake water, also increased bacterial uptake of Hg(II). These findings have several potential implications for mercury cycling, including effects on elemental mercury production, mercury sedimentation, and microbial methylation of Hg(II), and could be part of the explanation for the observed positive correlation between lake acidity and methyl mercury levels in fish.

Animals↗

Effects of licence change on prescribing and poisons enquiries for antipsychotic agents in England and Scotland.

AIMS: To examine the effect of licence change for thioridazine at the end of 2000 on the prescription of antipsychotic drugs in England and Scotland, and investigate changes in poisons information inquiries and, for Edinburgh, poisons admissions. METHODS: Prescription data for antipsychotic drugs were obtained for England and Scotland and quarterly trends examined for 2000 and 2001. Accesses to the UK National Poisons Information Service website TOXBASE for antipsychotic products were examined for the same period. For Scotland telephone enquiry data, and admission data to the Edinburgh Poisons Unit were also evaluated. Trends in poisonings were compared with prescribing change. RESULTS: In England prescriptions for thioridazine fell rapidly in 2001 from approximately 35% of market share to less than 5%, and were replaced by risperidone, chlorpromazine and olanzapine. TOXBASE accesses fell from 39.3% of antipsychotics to 4.4%. Accesses for chlorpromazine, olanzapine and risperidone increased. In Scotland prescribing of thioridazine was similar to changes in England, but it was principally replaced by chlorpromazine. These changes were mirrored by TOXBASE accesses, telephone enquiries and in-patient admissions. The ratio of TOXBASE accesses for thioridazine to prescription numbers for the drug increased after the licence change. CONCLUSIONS: Licence change produced rapid change in prescribing behaviour within 3 months. Prescribing behaviour in England and Scotland was different. Changes in prescribing were mirrored by changes in accesses for poisons information in both England and Scotland, and in Edinburgh by hospital admissions. The increase in the ratio of TOXBASE accesses to prescriptions for thioridazine suggests doctors may have become more aware of its potential toxicity.

Antipsychotic Agents↗

Adult respiratory distress syndrome and renal failure associated with citalopram overdose.

A 45-year-old man ingested 3000 mg of citalopram hydrobromide (2400 mg citalopram). He presented to the Emergency Department 2 hours post-ingestion with a pulse of 100 beats/min and blood pressure of 120/80 mmHg. His electrocardiogram (ECG) was normal. Chest X-ray showed bilateral shadowing, with no evidence of aspiration of gastric contents. Shortly after, he had three tonic-clonic seizures, requiring intravenous diazepam. Eight hours post-ingestion he became oliguric with deteriorating renal function, despite normal arterial and central venous pressures. He became increasingly hypoxic, with chest X-ray changes compatible with adult respiratory distress syndrome (ARDS). Despite treatment with 100% oxygen and continuous positive airway pressure, his gas exchange continued to deteriorate, requiring intubation and ventilation. His renal function also deteriorated with a peak creatinine of 492 micromol/L on day 4 in the absence of rhabdomyolysis. There was complete spontaneous recovery of renal function after 2 weeks. A peak plasma total citalopram (R+S enantiomers) concentration of 1.92 mg/L was recorded 2 hours post-ingestion. Total norcitalopram concentrations continued to rise up to 24 hours post-ingestion. Citalopram has been associated with seizures, ECG abnormalities, rhabdomyolysis and coma after overdose. The renal and respiratory complications seen in this patient have not been reported previously.

Citalopram↗

Polycyclic aromatic hydrocarbons in sediments, mussels and crustacea around a former gasworks site in Shoreham-by-Sea, UK.

Concentrations of polycyclic aromatic hydrocarbons have been determined in sediments, mussels and crustacea in the vicinity of a former gasworks site by Shoreham Harbour, UK. Very high concentrations of PAH were found in the substrate, an ash-like material deposited on the former gasworks site, which exhibited a profile consistent with the major source of contamination being coal or coke tar produced during the period of gas production at the site. Elevated PAH concentrations were also found in mussels both from the beach below the former gasworks site, and from sites further to the east in Portslade and Hove. The significance of these concentrations were assessed using an approach which involved the calculation of benzo[a]pyrene equivalent conoentrations (BaPEs), summing concentrations of individual PAH on the basis of their comparative potency as carcinogens. BaPE ranged from values of, or close to, zero for crustacea, to 336 microg kg(-1) wet weight in mussels from Southwick Beach. The contaminated mussels are not exploited commercially but may be taken by casual gatherers, and notices have been posted to warn potential consumers.

Animals↗

Randomised controlled trial of continuous positive airway pressure and standard oxygen therapy in acute pulmonary oedema; effects on plasma brain natriuretic peptide concentrations.

AIMS: The study aim was to compare the effects of continuous positive airway pressure (CPAP) on clinical outcomes and plasma neurohormonal concentrations in patients with acute pulmonary oedema. METHODS AND RESULTS: In addition to standard therapy, 58 consecutive patients were randomized to receive 60% inhaled oxygen with or without CPAP at 7.5 cmH(2)O pressure. Clinical variables, symptoms and oxygenation were monitored and plasma epinephrine, norepinephrine and brain natriuretic peptide (BNP) concentrations estimated at 0, 1, 6 and 24 h. CPAP was associated with less breathlessness at 1 h (P<0.001), no treatment failures and more rapid resolution in respiratory rate (P<0.001), heart rate (P<0.001) and acidosis (P<0.005). Length of hospital stay was similar but there was a trend for a reduction in overall hospital mortality in the CPAP group (0.10>P>0.05). Plasma BNP concentrations rose progressively (P<0.001) before falling below admission concentrations at 24 h. Plasma neurohumoral concentrations were unaffected by CPAP treatment but were elevated in patients who died or had acute myocardial infarction. CONCLUSION: CPAP produces a more rapid clinical and symptomatic improvement in patients with acute pulmonary oedema, particularly within the first hour. CPAP is a useful adjunctive treatment in the early management of acute heart failure.

Acute Disease↗

TOXBASE: poisons information on the internet.

OBJECTIVES: To assess the uptake, usage and acceptability of TOXBASE, the National Poisons Information Service internet toxicology information service. METHODS: An observational study of database usage, and a questionnaire of users were undertaken involving users of TOXBASE within the UK between August 1999, when the internet site was launched, and May 2000. The main outcome measures were numbers of registered users, usage patterns on the database, responses to user satisfaction questionnaire. RESULTS: The number of registered users increased from 567 to 1500. There was a 68% increase in accident and emergency departments registered, a 159% increase in general practitioners, but a 324% increase in other hospital departments. Between January 2000 and the end of May there had been 60 281 accesses to the product database, the most frequent to the paracetamol entry (7291 accesses). Ecstasy was the seventh most frequent entry accessed. Altogether 165 of 330 questionnaires were returned. The majority came from accident and emergency departments, the major users of the system. Users were generally well (>95%) satisfied with ease and speed of access. A number of suggestions for improvements were put forward. CONCLUSIONS: TOXBASE has been extensively accessed since being placed on the internet (http://www.spib.axl.co.uk). The pattern of enquiries mirrors clinical presentation with poisoning. The system seems to be easily used. It is a model for future delivery of treatment guidelines at the point of patient care.

Databases, Factual↗

Importance of the forest canopy to fluxes of methyl mercury and total mercury to boreal ecosystems.

The forest canopy was an important contributor to fluxes of methyl mercury (MeHg) and total mercury (THg) to the forest floor of boreal uplands and wetlands and potentially to downstream lakes, at the Experimental Lakes Area (ELA), northwestern Ontario. The estimated fluxes of MeHg and THg in throughfall plus litterfall below the forest canopy were 2 and 3 times greater than annual fluxes by direct wet deposition of MeHg (0.9 mg of MeHg ha(-1)) and THg (71 mg of THg ha(-1)). Almost all of the increased flux of MeHg and THg under the forest canopy occurred as litterfall (0.14-1.3 mg of MeHg ha(-1) yr(-1) and 110-220 mg of THg ha(-1) yr(-1)). Throughfall added no MeHg and approximately 9 mg of THg ha(-1) yr(-1) to wet deposition at ELA, unlike in other regions of the world where atmospheric deposition was more heavily contaminated. These data suggest that dry deposition of Hg on foliage as an aerosol or reactive gaseous Hg (RGM) species is low at ELA, a finding supported by preliminary measurements of RGM there. Annual total deposition from throughfall and litterfall under a fire-regenerated 19-yr-old jack pine/birch forest was 1.7 mg of MeHg ha(-1) and 200 mg of THg ha(-1). We found that average annual accumulation of MeHg and THg in the surficial litter/fungal layer of soils since the last forest fire varied between 0.6 and 1.6 mg of MeHg ha(-1) and between 130 and 590 mg of THg ha(-1) among sites differing in drainage and soil moisture. When soil Hg accumulation sites were matched with similar sites where litterfall and throughfall were collected, measured fluxes of THg to the forest floor (sources) were similar to our estimates of longterm soil accumulation rates (sinks), suggesting that the Hg in litterfall and throughfall is a new and not a recycled input of Hg to forested ecosystems. However, further research is required to determine the proportion of Hg in litterfall that is being biogeochemically recycled within forest and wetland ecosystems and, thus, does not represent new inputs to the forest ecosystem.

Aerosols↗