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Biomedical subjects

A Jardine

Publications and source records attributed to A Jardine.

At least 19 recordsLinked to original sources

A multivariate analysis of the factors predicting hearing outcome after surgery for cholesteatoma in children.

OBJECTIVE: To explore factors influencing hearing outcomes in children treated by canal wall up (CWU) and canal wall down (CWD) mastoid surgery. METHODS: Retrospective cohort study including three units in Bristol and Bath, UK. Ninety consecutive children underwent cholesteatoma mastoid surgery, with the first procedure between 1998 and 2001; minimum follow up was three disease-free years. RESULTS: The CWU and CWD cohorts significantly differed in pre-operative stage and hearing. After disease eradication, air conduction (AC) thresholds changed by +4.0 dB (95 per cent confidence intervals (95% CI) -2.0, 10.1) in the CWD group and -5.3 dB (95% CI -9.3, 1.3) in the CWU group (p=0.029). Using multiple linear regression to account for cohort differences, AC thresholds were increased by: pre-operative AC threshold (p<0.0001), initial ossicular stage (p=0.013), and CWD-surgery (p=0.005). CONCLUSION: Disease-free hearing was better with CWU-surgery, less initial ossicular damage, and better pre-operative hearing. Worse initial disease increased the likelihood of CWD surgery. Wider use of ossiculoplasty in the CWU cohort (51 per cent vs 5 per cent) may partially explain the superior results.

Adolescent↗

Analysis of the 5' flanking region of the interleukin 10 gene in patients with systemic sclerosis.

OBJECTIVES: Fibrosis, a feature of systemic sclerosis (SSc), is more severe in the diffuse compared with the limited disease variant. Interleukin 10 (IL-10) is an anti-inflammatory cytokine which reduces type 1 collagen mRNA levels in human fibroblasts. The 5' flanking region of the IL-10 gene is highly polymorphic, with three single base pair substitutions at position -1082(G/A), -819(C/T) and -592(C/A), which results in differential IL-10 production. The GCC/GCC genotype is associated with high IL-10 production while the ATA/ATA genotype with low production. We postulated that there would be a difference in IL-10 polymorphisms in patients with limited (lSSc) and diffuse (dSSc) disease. METHODS: Patients with limited (lSSc, n = 89) or diffuse (dSSc, n = 51) disease plus controls (n = 94) were recruited. DNA was isolated from peripheral blood and polymorphisms analysed using amplification refractory mutation system (ARMS) polymerase chain reaction (PCR). RESULTS: dSSc patients were less likely to carry the genotype indicative of high IL-10 production when compared with controls (controls vs dSSc; 29 vs 4%, chi2 = 15.7, 5 df, P = 0.005) and lSSc patients (lSSc vs dSSc; 21 vs 4%, chi2 = 17.5, 5 df, P = 0.002). There was no difference between control and lSSc patients. While there was no difference between controls and lSSc haplotypes, the GCC haplotype distribution did differ significantly between controls and dSSc patients (controls vs dSSc; 54 vs 36%, chi2 = 11.2, 2 df, P = 0.001). A significant difference was also observed between lSSc and dSSc haplotype distribution (lSSc vs dSSc; 48 vs 36%, chi2 = 13.5, 2 df, P < 0.001). CONCLUSION: We demonstrate that IL-10 genotypes associated with high IL-10 production are under-represented in dSSc. This may have implications in the disease pathology.

DNA↗

Acute renal allograft rejections, a role for statins?

Acute rejection of kidney allografts during the first months following transplantation is one of the most important risk factor for long-term graft failure. Some small open studies have indicated that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-Co-A), statins, might act as immunosuppressive agents, and reduce acute rejection rates. Moreover, the use of statin in transplant recipients is quite common, despite no data from prospective large multi-centre studies are available to demonstrate any beneficial effect for acute rejections or long-term cardiovascular protection in this population. In this overview, recent clinical and experimental data will be provided for assessing statins as immunosuppressive agents. Although in vitro studies have provided a theoretical basis for the use of statins as immunosuppressive agents, more recent clinical placebo controlled studies have failed to confirm the initial optimism of this effect of statins.

Acute Disease↗

Analysis of transforming growth factor beta1 gene polymorphisms in patients with systemic sclerosis.

OBJECTIVES: To determine the distribution of transforming growth factor beta1 (TGFbeta1) genotypes at codon 10 (+869 polymorphism) and codon 25 (+915 polymorphism) in patients with scleroderma (SSc). Differences between diffuse and limited SSc (dSSc and lSSc) were also investigated. METHODS: Patients with lSSc (n=89) and dSSc (n=63) were compared with 147 controls. DNA was isolated from peripheral blood and polymorphisms at codons 10 (C/T) and 25 (G/C) of the TGFbeta1 gene analysed by polymerase chain reaction and sequence specific oligonucleotide probing. RESULTS: Significantly more patients with SSc than controls carried allele C at codon 10 (controls v SSc, 38% v 48%, chi(2)=8.2, 1df, p=0.004), OR=1.95 (95% CI 1.16 to 3.27). The difference remained when patients with SSc were split into those with limited or diffuse disease, (controls v dSSc, chi(2)=5, 1df, p=0.02 and controls v lSSc, chi(2)=6, 1df, p=0.013). The patients with SSc had significantly more subjects heterozygous at codon 10 (controls v SSc, chi(2)=45, 1df, p<0.0001). Possession of allele C at codon 10 gave an OR=4.8 (95% CI 2.8 to 8.4). No difference in allele frequency was seen between patients with SSc and controls at codon 25. More patients with SSc than controls carried the GG genotype (controls v SSc, 80% v 88%, chi(2)=7, 2df, p=0.027). Possession of allele G gave an OR=1.7 (95% CI 0.5 to 5.9). There was no difference between diffuse and limited disease at either codon. CONCLUSIONS: These results suggest that patients with SSc are genetically predisposed to high TGFbeta1 production. These polymorphisms do not, however, explain the difference in the clinical phenotypes of limited and diffuse SSc.

Codon↗

Intraoperative motor evoked potentials to transcranial electrical stimulation during two anaesthetic regimens.

OBJECTIVES: To study motor evoked potentials (MEPs) to multi-pulse transcranial electrical stimulation (MP-TES) during orthopaedic spinal surgery under different anaesthetic regimens. METHODS: MEPs to MP-TES were recorded from tibialis anterior and abductor hallucis bilaterally in 50 operations. Anaesthesia was maintained with propofol and nitrous oxide in 29 operations and isoflurane (0.78+/-0.17% end-tidal) and nitrous oxide in 23 (two patients received both regimens). Analgesia was provided with fentanyl or remifentanil. RESULTS: Motor stimulation caused neither EEG changes nor seizures. MEPs were obtained in 97% of patients during propofol anaesthesia. The median amplitude and coefficient of variation (CV) at baseline (across all muscles) were 198 microV and 22%, respectively. Amplitudes throughout the operation paralleled the degree of neuromuscular block and were reduced after fentanyl bolus, isoflurane or morphine. Loss of MEPs or persistent amplitude decrements were associated with neurological complications in one patient and severe blood loss in another two patients. MEPs were obtainable in 61% of patients during isoflurane anaesthesia and became inconsistent for end-tidal concentrations >0.87+/-0.08%. Amplitudes were smaller (85 microV) and baseline variability higher (coefficient of variation 29%) than in the propofol group. The decrease in the number of recordings was greater for isoflurane than propofol when the number of pulses/train decreased from 4 to 2. CONCLUSIONS: Muscle MEPs to MP-TES are a safe, sensitive and reliable method for monitoring motor pathways during propofol/nitrous oxide and fentanyl or remifentanil anaesthesia. MEPs are also obtainable in the majority of patients during isoflurane/nitrous oxide anaesthesia, but quantitative monitoring is not always possible with this regimen.

Adolescent↗

The effects of litigation on symptom expression: a prospective study following mild traumatic brain injury.

OBJECTIVE: To prospectively assess the association between litigation and neurobehavioural symptoms following mild Traumatic Brain Injury (TBI). DESIGN: a prospective study with the inception cohort assessed on average 42.2(17.2) days after injury. SETTING: an outpatient clinic within a large general hospital. PATIENTS: a consecutive sample of 100 clinic attenders with mild TBI. OUTCOME MEASURES: A cognitive screen (Mini-Mental State Examination (MMSE), Galveston Orientation and Amnesia Test (GOAT), a measure of psychological distress (the 28 item General Health Questionnaire (GHQ)) and two head injury outcome measures, the Glasgow Outcome Scale (GOS) and the Rivermead Head Injury Follow-up Questionnaire (RHFUQ). RESULTS: Demographic characteristics, TBI severity ratings and premorbid risk factors for poor outcome did not differ between litigants (27.8 per cent of the sample) and non-litigants. However, litigants were significantly more anxious (p<0.0001), depressed (p<0.01), had greater social dysfunction (p<0.0001) and had poorer outcome on the GOS (p<0.002) and RHFUQ (p<0.002). There were no cognitive differences between the groups. CONCLUSIONS: the data demonstrate an association between litigation and increased psychological distress at the outset of the litigation process. While association is not synonymous with causality, the absence of demographic, premorbid and TBI related differences between litigants and non-litigants suggests that the pursuit of compensation may influence the subjective expression of symptoms following mild traumatic brain injury.

Adult↗

Effects of fluvastatin on cardiac events in renal transplant patients: ALERT (Assessment of Lescol in Renal Transplantation) study design and baseline data.

BACKGROUND: Recent clinical trials of primary and secondary prevention of cardiovascular disease have demonstrated that lowering plasma cholesterol with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors ('statins') reduces morbidity and mortality from coronary heart disease in diverse patient populations. STUDY AIMS: The aim of the present ALERT (Assessment of Lescol in Renal Transplantation) study is to determine whether renal transplant recipients would also benefit from statin therapy. ALERT is a multicentre, randomized, double-blind, placebo-controlled trial to assess the effect of fluvastatin in renal transplant recipients with mild-to-moderate hypercholesterolaemia. The primary objective is to investigate the effects of fluvastatin on major adverse cardiac events (MACE). In addition, the effects on cardiovascular and all-cause mortality, as well as renal function, will be addressed. STUDY POPULATION: The study population contains patients with functioning renal allografts of more than 6 months' duration, recruited from 75 centres in Northern Europe and Canada. Patients of both sexes, aged 30-75 years, with a total cholesterol level of 4.0-9.0 mmol/l (155-348 mg/dl) were included, except for those with a history of myocardial infarction, where the upper limit for inclusion was 7.0 mmol/l (270 mg/dl). STUDY DESIGN: A total of 2100 patients were recruited by the end of October 1997 and will be followed for up to 6 years. This report presents the design features of the study (recruitment, follow-up, sample size, data analysis and study organization), along with baseline results. ALERT is the first large-scale prospective, randomized, double-blind study to address the prevention of cardiovascular mortality in renal transplant patients receiving an HMGCoA reductase inhibitor.

Adult↗

Fluvastatin in combination with cyclosporin in renal transplant recipients: a review of clinical and safety experience.

Cardiovascular disease remains a significant cause of morbidity and mortality in patients who have undergone renal transplantation, with one of the main risk factors being post-transplantation hyperlipidaemia. To date, however, optimal management of elevated lipid levels in such patients has been hindered by the lack of both effective and safe treatments, coupled with concerns over probable interactions with immunosuppressive therapy, particularly cyclosporin. Numerous studies confirm that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, such as fluvastatin, are effective lipid-lowering agents in renal transplant recipients, supporting findings in other patients' groups. Moreover, based on investigations of metabolic profile and clinical observation, fluvastatin (at dosages of up to 80 mg/day) is well tolerated in renal transplant recipients receiving cyclosporin. In clinical trials to date, no instances of rhabdomyolysis have been observed during co-administration of fluvastatin and cyclosporin. The potential of fluvastatin for improving survival in renal transplant recipients, in terms of both cardiovascular mortality and graft rejection, is currently being investigated in two ongoing studies: ALERT (Assessment of Lescol [fluvastatin] in Renal Transplantation) and SOLAR (Study of Lescol [fluvastatin] in Acute Rejection). The results of these landmark studies should confirm the safe utility of fluvastatin in the renal transplantation setting.

Anticholesteremic Agents↗

Neurological complications of anterior spinal surgery for kyphosis with normal somatosensory evoked potentials (SEPs).

We report a case of neurological complications of anterior release for correction of kyphosis. After the operation, the patient had pyramidal weakness and decreased pain sensation below T5, whereas light touch, proprioception and vibration sensation were intact. Clinical and neurophysiological findings in this patient suggested a partial lesion of the spinal cord probably due to ischaemia in the territory of the anterior spinal artery. Intraoperative and postoperative tibial nerve SEPs remained normal, which stresses the need for recording from the motor pathways.

Adult↗

Contralateral pneumothorax following thoracotomy for vertebrectomy.

A 21-year-old woman underwent correction of congenital thoracic kyphoscoliosis. The procedure was completed in two stages. The first stage involved right thoracotomy and anterior vertebrectomy. Following positional obstruction of her right-sided chest drain she developed a very large, left-sided pneumothorax in the immediate postoperative period. No attempt at central venous line placement had been made on the left side. Breach of the midline at vertebrectomy may allow pleural gas to cross and cause a contralateral pneumothorax.

Adult↗

Cardiopulmonary complications during anaesthesia and surgery for severe thoracic lordoscoliosis.

A 15-year old girl underwent a posterior spinal fusion procedure for severe lordoscoliosis. On turning to the prone position acute posture-related upper airway obstruction occurred. During surgery, manipulation of the spine caused several episodes of loss of cardiac output. Retrospective assessment of the pre-operative chest X rays demonstrated approximation of the sternum and thoracic vertebrae, with evidence of tracheal narrowing at the level of the thoracic inlet. We feel that both complications were directly related to the severity of the lordoscoliosis and that careful pre-operative clinical, spirometric and X ray assessment should be undertaken in such patients.

Adolescent↗

Case report: pancreatic mediastinal pseudocyst--an unusual cause of palpitations.

We describe a case of pancreatic mediastinal pseudocyst which presented atypically with palpitations due to marked cardiac compression. Computed tomography (CT) showed a large abdominal pseudocyst extending through the diaphragm into the posterior mediastinum. Surgical drainage produced rapid symptomatic relief and the pseudocyst resolved completely within 2 months.

Arrhythmias, Cardiac↗

Foetal warfarin syndrome--a complex airway problem. Case report and review of the literature.

Premature cartilaginous calcification and nasal hypoplasia following first trimester exposure to warfarin are known as the Foetal Warfarin Syndrome (FWS). There are over 40 cases reported in the literature, many of which describe breathing and feeding difficulties in the first few months of life. We report a case where a child had had difficulties breathing and feeding in the first months of life. These had been attributed to nasal hypoplasia. After proper ENT assessment the child benefitted from adenoidectomy. ENT surgeons should be aware of the syndrome as more women of child bearing age are taking warfarin following cardiac surgery and treatment of thromboembolic disease. ENT surgeons may be asked to review these children who often present with airway and feeding problems which have been attributed to nasal hypoplasia.

Calcinosis↗

Increased circulating atrial natriuretic factor concentrations in patients with chronic heart failure after inhibition of neutral endopeptidase: effects on diastolic function.

OBJECTIVE: +/- Candoxatrilat was used to raise atrial natriuretic factor (ANF) concentrations in patients with heart failure, and the effects on left ventricular systolic and diastolic function were studied to determine the contribution of peripheral and central mechanisms to the haemodynamic effects. DESIGN: This was a single blind, randomised comparison of +/- candoxatrilat and placebo in patients with mild heart failure. All patients received two intravenous doses of +/- candoxatrilat and two placebo doses on four consecutive days. SETTING: A teaching hospital department of cardiology. PATIENTS: Six men (mean age 52 years) with mild heart failure (New York Heart Association class II) due to ischaemic heart disease (four patients) or dilated cardiomyopathy (two patients) were included. Mean ejection fraction was 37.5% and mean peak oxygen consumption was 20.4 ml/min/kg. MAIN OUTCOME MEASURES: Plasma ANF concentrations, haemodynamic indices and left ventricular diastolic function measured by early to atrial filling rate (E:A ratio) with Doppler echocardiography were determined before and after +/- candoxatrilat and placebo. RESULTS: +/- Candoxatrilat caused a threefold rise of plasma ANF compared with placebo (p < 0.005), but there was no significant change in heart rate, blood pressure, or cardiac output. Mean right atrial pressure fell from 6.7 to 4.7 mmHg (NS) and pulmonary artery wedge pressure fell from 9.2 to 6.7 mmHg (p < 0.05). Doppler echocardiographic measurements of transmitral blood flow showed a significant fall in peak early left ventricular filling velocity from 39.5 to 34.2 cm/s (p < 0.05), along with a non-significant rise in peak atrial filling velocity from 39.7-41.6 cm/s after +/- candoxatrilat. The E:A ratio, a Doppler index of left ventricular diastolic function, fell from a mean of 1.04 to 0.87 (p < 0.05). CONCLUSIONS: +/- Candoxatrilat increased plasma ANF concentrations and reduced right atrial and pulmonary artery wedge pressures. No evidence of an improvement in left ventricular systolic or diastolic function was found, so the fall in preload was due to peripheral effects, either an increase in venous capacitance or a fall in circulating blood volume.

Atrial Natriuretic Factor↗

Plasma endothelinlike immunoreactivity levels in IDDM patients with microalbuminuria.

OBJECTIVE: To determine whether plasma endothelin, a potent vasoconstrictor and growth factor for vascular smooth muscle, is elevated in microalbuminuric insulin-dependent diabetes mellitus patients. RESEARCH DESIGN AND METHODS: Plasma endothelinlike immunoreactivity was measured by radioimmunoassay in 15 microalbuminuric diabetic patients, 12 normoalbuminuric diabetic patients, and 12 control subjects. RESULTS: The mean levels of plasma endothelinlike immunoreactivity were raised in the normoalbuminuric patients (8.4 pM [range 4.8-12.7 pM]; P less than 0.01) and the microalbuminuric patients (10.2 pM [range 5.6-31.1 pM]; P less than 0.001) compared with control subjects (6.1 pM [range 4.5-7.6 pM]). Plasma endothelinlike immunoreactivity was also higher in the microalbuminuric patients compared with the normoalbuminuric patients (P less than 0.05). CONCLUSIONS: The increase in plasma endothelinlike immunoreactivity further confirms endothelial dysfunction in diabetes and this increase in plasma endothelin may contribute to the vascular disease prevalent in diabetes.

Adult↗

Interaction of angiotensin II and atrial natriuretic peptide in the human fetoplacental unit.

We have identified two classes of membrane receptor for atrial natriuretic peptide (KD (dissociation constant) 0.2, 70.1 nmol/L) and angiotensin II (KD 1.7 nmol/L, 15.2 nmol/L) in human fetoplacental vasculature. In addition, in the isolated perfused placenta atrial natriuretic peptide inhibited the vasoconstrictor action of angiotensin II. These findings suggest that atrial natriuretic factor may regulate fetoplacental blood flow.

Angiotensin II↗