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Biomedical subjects

J Sykes

Publications and source records attributed to J Sykes.

At least 19 recordsLinked to original sources

Rapid onset of effect of sodium alginate on gastro-oesophageal reflux compared with ranitidine and omeprazole, and relationship between symptoms and reflux episodes.

The objective of the open, randomised, four-period crossover study was to compare the time of onset of effect of sodium alginate (SA), omeprazole, ranitidine and control, based on oesophageal and intragastric pH and to determine any correlation between reflux symptoms and episodes in volunteers suffering from occasional gastro-oesophageal reflux. SA showed extensive prevention of acid exposure in the oesophagus compared with other treatments during the first hour. Overall, SA was more effective than control or omeprazole and comparable with ranitidine. There was little evidence of association between 'oesophageal' symptoms and reflux episodes, but associations between 'gastric' symptoms and acidity in the oesophagus, fundus and corpus were apparent. For an immediate reduction in gastro-oesophageal reflux into the oesophagus and gastric acidity during the first hour, SA was significantly superior to control, ranitidine and omeprazole. Ranitidine showed a superior effect from 2 h, consistent with its pharmacological mode of action.

Adolescent↗

Alginate rafts and their characterisation.

Alginate/antacid anti-reflux preparations are designed to provide symptom relief by forming a physical barrier on top of the stomach contents in the form of a neutral floating gel or raft. This study tested the in vitro effectiveness of a range of liquid products in forming rafts that were cohesive, buoyant, voluminous, resistant to reflux and durable under conditions of movement (resilient). The products tested had a wide range of acid neutralising capacities (ANCs). It was found that products with a high ANC and no calcium ion source formed rafts of low strength, weight and volume, which appeared more as floating precipitates than coherent gels. Products with a high ANC and a calcium ion source formed medium strength, weight and volume rafts. Products with a low ANC formed strong coherent rafts with medium to large weight and volume, and those with low ANC and a calcium ion source formed the strongest rafts. Products with stronger rafts were found to be more resilient and more resistant to reflux in an in vitro reflux model. Significant overall differences in raft buoyancy were found between products forming coherent rafts but these could not be related to the product formulation or amount of available carbon dioxide.

Alginates↗

An assessment of clinically optimal gold marker length and diameter for pelvic radiotherapy verification using an amorphous silicon flat panel electronic portal imaging device.

Verification of target organ position is essential for the accurate delivery of conformal radiotherapy. Megavoltage electronic portal imaging with flat panel amorphous silicon detectors delivers high quality images that can be used for verification of bony landmark position. Gold markers implanted into the target organ can be visualized and used as a surrogate of actual organ position. On-line compensation for marker displacement, by adjusting patient position, can reduce geometric errors associated with radiation delivery. This study assesses the optimal marker length and diameter to be used with an amorphous silicon (a-Si) flat panel detector and electronic portal images (EPIs), prior to implementation of a clinical programme of gold marker insertion in prostate cancer patients. Seven marker sizes varying from 3 mm to 8 mm in length and 0.8 mm to 1.1 mm in diameter were investigated in a group of patients undergoing pelvic radiotherapy using an 8 MV Elekta SL20 linear accelerator. Markers were placed on the skin entry and exit sites of the treatment beam and EPIs in both lateral and anterior pelvic views were acquired. Three observers independently assessed visibility success and failure using a subjective scoring system. Markers less than 5 mm in length or 0.9 mm in diameter were poorly visualized (<70% visualization success in lateral EPIs). The marker measuring 0.9 mm x 5 mm appears to be clinically optimal in pelvic radiotherapy patients (80% visualization success in lateral EPIs) and will be used for actual organ implantation.

Electronics, Medical↗

An RCT pilot study to test the effects of intravenous midazolam as a conscious sedation technique for anxious children requiring dental treatment--an alternative to general anaesthesia.

AIM: To add to the evidence base for acceptable and effective paediatric conscious sedation techniques in dental primary care. OBJECTIVES: To compare three conscious sedation techniques for primary care as an alternative to dental general anaesthesia (DGA) in children. To assess the feasibility and practicality of running the trial in general dental practice. To form the basis for sample size calculations and assess scales of measurement. DESIGN: Single centre, randomised control trial (RCT). SETTING: Queensway Anxiety Management Clinic (QAMC). A primary care based general and referral dental practice for the management of anxious patients. SUBJECTS, MATERIALS AND METHODS: Sixty five children too anxious for management with relative analgesia, requiring invasive dental procedure for which dental general anaesthesia (DGA) will be required if an alternative cannot be found. INTERVENTIONS: Group 1 (n = 20) - A combination of inhaled medical air and titrated intravenous midazolam. Group 2 (n = 22) - A combination of inhaled 40% nitrous oxide in oxygen and titrated intravenous midazolam. Group 3 (n = 23) - A combination of an inhaled mixture of 0.3% sevoflurane and 40% nitrous oxide in oxygen with titrated intravenous midazolam. MAIN OUTCOME MEASURES: Successful completion of the intended dental treatment with a child who is co-operative and responsive to verbal commands. RESULTS: Fifty per cent (ten children) successfully completed treatment in Group 1, 73% (16 children) in Group 2 and 83% (19 children) in Group 3. This difference was not significant at a 5% level (chi(2) = 5.53, df = 2, P = 0.07) Of the total of 20 failures, eight children in Group 1 and one child in Group 2 were successfully treated with the addition of sevoflurane and nitrous oxide in oxygen. Only two children required referral to a hospital setting for DGA and the remaining nine children were managed with an alternative conscious sedation technique. CONCLUSION: This pilot shows that intravenous midazolam especially in combination with the addition of inhaled nitrous oxide or sevoflurane and nitrous oxide were promising safe and effective techniques, sufficient to justify progression to a definitive RCT with appropriate methods.

Adolescent↗

Disseminated infection with Balamuthia mandrillaris in a dog.

Bilateral chronic granulomatous nephritis and meningoencephalitis were diagnosed on necropsy of a 2-year-old male Great Dane dog. The causative agent was identified as Balamuthia mandrillaris, based on morphologic features, immunohistochemical staining, and deoxyribonucleic acid detection using the polymerase chain reaction with newly designed primer pairs. Trophozoite and cystic forms of the amoeba were evident within the kidneys and brain parenchyma. This is the first report on a B. mandrillaris infection in a dog.

Animals↗

An investigation into the comparative efficacy of soluble aspirin and solid paracetamol in postoperative pain after third molar surgery.

OBJECTIVE: To compare the efficacy of soluble aspirin 900 mg and paracetamol 1,000 mg in patients with postoperative pain after third molar surgery. DESIGN: A randomised, placebo controlled, double-blind study. SETTING: Day stay units of Oral and Maxillofacial Surgery at Cardiff Dental Hospital and Hexham General Hospital, Northumberland. SUBJECTS AND METHODS: One hundred and sixty-seven (104 female) patients who required the removal of their impacted third molars under general anaesthesia. INTERVENTION: In the early postoperative period, patients were medicated with either a single dose of soluble aspirin 900 mg, solid paracetamol 1,000 mg or placebo. MAIN OUTCOME MEASURES: Pain intensity was measured on 100 mm visual analogue scales at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120 and 240 minutes after dosing. Other efficacy variables evaluated included time to rescue medication and an overall assessment of the study medication efficacy by the patient on completion of the study. RESULTS: One hundred and sixty-seven patients consented to take part in the study, but only 153 were medicated. Of the 14 patients not treated, 10 failed to develop sufficient pain to enter the study, two withdrew consent, one had an adverse reaction to the general anaesthetic and one was a protocol violator. Over the four hour investigation period, patients treated with soluble aspirin reported significantly less pain when compared with those treated with paracetamol (mean difference in AUC(0-240) = -2001, 95% CI -3893 to -109, p=0.038) and placebo (mean difference in AUC(0-240) = -3470, 95% CI -5719 to -1221, p=0.003). Similarly, at 20 and 30 minutes after dosing, patients in the soluble aspirin group were reporting significantly less pain than those in the paracetamol treatment group (mean difference in pain intensity: at 20 minutes -7.9, 95% CI -15.3 to -0.6, p=0.035; at 30 minutes -10.6, 95% CI -18.6 to -2.6, p=0.010). There were no significant differences between treatment groups with respect to the number of patients requiring rescue medication, however the time to dosing was significantly longer for those taking soluble aspirin when compared with placebo (hazard ratio 2.34, 95% CI 1.41 to 3.88, p<0.001). CONCLUSION: The findings from this study showed that soluble aspirin 900 mg provides significant and more rapid analgesia than paracetamol 1,000 mg in the early postoperative period after third molar surgery.

Acetaminophen↗

An investigation of the toxicity of gadolinium based MRI contrast agents using neutron activation analysis.

The toxicity of gadolinium (Gd) based MRI contrast agents, is based upon the amount of Gd that dissociates from its chelate and deposits in tissues. In this study, the toxicities of two contrast agents were tested using different injection strategies in two animal models. Following a bolus injection of 0.2 mmol/kg of Gd-DTPA in a pilot study with a single canine, Gd levels were as high as 2.05 +/- 0.17 ppm and 0.47 +/- 0.11 ppm 2 weeks post injection in the kidney and liver tissues, respectively. To evaluate the role that the injection strategy plays in toxicity, 0.8 mmol/kg of Gd-(HP-DO3A) was injected into rats, in a second study, via bolus and constant infusion techniques. Gd was only detected in the kidney in the bolus injected rats but in the lung as well in the constant infusion injected rats. Concentrations detected in the kidney for both strategies, were comparable within error: 1.37 +/- 0.46 ppm for the bolus and 1.24 +/- 0.39 ppm for the bolus/constant infusion strategy and 0.16 +/- 0.14 ppm in the lung for the constant infusion technique. The contrast infusion technique does not appear to present an increased risk of toxicity over the bolus technique except perhaps to a small degree in the lung.

Animals↗

An open-label, multicentre study to assess the safety and efficacy of a novel reflux suppressant (Gaviscon Advance) in the treatment of heartburn during pregnancy.

This study investigated the efficacy and safety of a novel reflux suppressant, Gaviscon Advance, in the treatment of heartburn during pregnancy. The study was an open-label, multicentre, phase IV study in general practice and antenatal clinics in the UK and Republic of South Africa. Pregnant women (< or = 38 weeks gestation; n=150) aged 18-40 years suffering from heartburn were instructed to take Gaviscon Advance 5-10 ml, as required, to relieve symptoms. The main outcome measures were the efficacy rating of the study medication by the investigator and women after four weeks using a five-point efficacy scale. After four weeks the investigators' and women's rating of efficacy was 'very good' or 'good' in 88% and 90% of women, respectively. Most women (57%, n=83) reported symptom relief within 10 minutes. Thus Gaviscon Advance effectively and rapidly treats heartburn during pregnancy. Its use during pregnancy presents no known significant safety concerns for mother or child.

Adolescent↗

The imPaCT study: a randomised controlled trial to evaluate a hospital palliative care team.

A randomised controlled trial was undertaken to assess the effectiveness of a hospital Palliative Care Team (PCT) on physical symptoms and health-related quality of life (HRQoL); patient, family carer and primary care professional reported satisfaction with care; and health service resource use. The full package of advice and support provided by a multidisciplinary specialist PCT ('full-PCT') was compared with limited telephone advice ('telephone-PCT', the control group) in the setting of a teaching hospital trust in the SW of England. The trial recruited 261 out of 684 new inpatient referrals; 175 were allocated to 'full-PCT', 86 to 'telephone-PCT' (2 : 1 randomisation); with 191 (73%) being assessed at 1 week. There were highly significant improvements in symptoms, HRQoL, mood and 'emotional bother' in 'full-PCT' at 1 week, maintained over the 4-week follow-up. A smaller effect was seen in 'telephone-PCT'; there were no significant differences between the groups. Satisfaction with care in both groups was high and there was no significant difference between them. These data reflect a high standard of care of patients dying of cancer and other chronic diseases in an acute hospital environment, but do not demonstrate a difference between the two models of service delivery of specialist palliative care.

Activities of Daily Living↗

Myocardial viability imaging using Gd-DTPA: physiological modeling of infarcted myocardium, and impact on injection strategy and imaging time.

Results of simulations are shown which illustrate how the concentration-time curves of an extravascular extracellular (EVEC) contrast agent, such as Gd-DTPA, vary in myocardial tissue. The simulations show that the variable permeability of dead myocytes within a recent myocardial infarction will significantly alter delayed enhancement patterns following a bolus injection, invariably reducing the sensitivity of this technique for the detection of permanently damaged tissue. It is further predicted that if the bolus injection is followed by a suitably selected constant infusion, the infarct size and infarct volume of distribution may be more accurately determined, even though the degree of enhancement of an infarcted region (with normal flow) above normal tissue is slightly higher for the bolus technique within the first 30 min following the injection. The degree of enhancement of an infarcted region (with normal flow) above normal tissue was comparable between the two techniques at the point in the constant infusion at which the volume of contrast injected was the same as in the bolus case, i.e., at approximately 30 min after the bolus injection. The constant infusion approach became superior thereafter as overall tissue concentrations became greater in both normal and infarcted tissue, and these concentrations remained more stable with the constant infusion approach. Preliminary experimental results in a canine model of infarction/reperfusion illustrated a delayed wash-in of contrast agent in infarcted tissue, which may be explained by a physiological model in which dead myocytes in infarcted myocardium have non-infinite permeability.

Animals↗

Examining a canine model of stunned myocardium with Gd-DTPA-enhanced MRI.

It has previously been shown that the distribution volume of Gd-DTPA (lambda) in infarcted, canine myocardium is higher than that of normal tissue. The purpose of this study was to determine whether stunned myocardium exhibits increased lambda. Stunning was produced in beagles by means of 30 min LAD occlusion followed by 3 weeks (n = 4) reperfusion. Gd-DTPA was infused at each imaging session and lambda determined in vivo using a saturation recovery turboFLASH sequence; cine imaging was used to assess ventricular wall thickening (%WT). (201)Tl uptake was used as an independent assessment of viability. %WT data confirmed that the brief insult caused prolonged, yet reversible, regional contractile dysfunction in each animal. %WT was not significantly different from baseline values by 3 weeks post-reflow. Normal (201)Tl uptake confirmed the absence of infarction. The lambda of stunned tissue (lambda = 0.381 +/- 0.030 ml/g) was not elevated above that of normal tissue (lambda = 0.398 +/- 0.027 ml/g, P = NS), at any time point studied, in vivo. These data suggest that an increase in lambda is a specific indicator of irreversible damage.

Animals↗

Gd-DTPA bolus tracking in the myocardium using T1 fast acquisition relaxation mapping (T1 FARM).

MRI methods currently used for bolus tracking in the myocardium, such as saturation recovery turbo-fast low-angle shot (FLASH) (srTFL), are limited by signal intensity (SI) saturation at high contrast agent (CA) concentrations. By using T1 fast acquisition relaxation mapping (T1 FARM), a Gd-DTPA bolus (0.075 vs. 0.025 mmol/kg) may be injected without causing saturation. This study tested the feasibility of in vivo T1 FARM bolus tracking under rest/stress conditions in seven beagles with multiple permanently occluded branches of the left anterior descending (LAD) coronary artery. Although it underestimated the myocardial perfusion reserve (MPR) measured ex vivo using radioactive microspheres (mean +/- SEM; 3.60 +/- 0.26), the MPR determined upon application of the modified Kety model (1.86 +/- 0.10) enabled distinction between normal and infarcted tissue. The partition coefficient (lambda) estimated at rest and stress using the modified Kety model underestimated ex vivo radioactive measurements in infarcted tissue (0.25 +/- 0.01 vs. 0.26 +/- 0.01 vs. 0.79 +/- 0.08 ml/g, P < 0.0001) yet was accurate in normal tissue (0.28 +/- 0.01 vs. 0.30 +/- 0.01 vs. 0.33 +/- 0.01 ml/g, P = NS). Thus, although unsuitable for myocardial viability assessment, T1 FARM bolus tracking shows potential for assessment of myocardial perfusion.

Animals↗

The use of Gd-DTPA as a marker of myocardial viability in reperfused acute myocardial infarction.

At present, accurate assessment of the extent of myocardial viability after acute myocardial infarction is limited due to the spatial resolution of currently available imaging modalities. MR cardiac imaging, with its superior spatial resolution, would be used if viable and infarcted tissue could be separated based on signal intensity. In infarcted tissue, cell membrane breakdown allows the entry of the MR contrast agent Gd-DTPA which is normally extracellular. The increased space for Gd-DTPA distribution (partition coefficient, lambda) in this infarcted tissue results in increased Gd-DTPA concentration and hence increased signal intensity on T1-weighted MR images. In a canine model of ischemia/reperfusion injury, the partition coefficient in infarcted tissue increased as early as 1 min post reperfusion. lambda in infarcted tissue stayed increased over that in normal tissue for at least 8 weeks. The accuracy of contrast-enhanced MRI was confirmed by results of 201Tl SPECT and a cine MRI dobutamine wall motion study in a patient 1 week after an acute myocardial infarction. Thus, contrast-enhanced MRI shows great promise for the non-invasive determination of myocardial viability after acute myocardial infarction.

Animals↗

Simultaneous MRI measurement of blood flow, blood volume, and capillary permeability in mammary tumors using two different contrast agents.

A technique for the simultaneous measurement of three vascular parameters: blood flow (Frho), blood volume (v(b)), and the capillary permeability-surface area product (PSrho) in breast tumors using dynamic contrast-enhanced magnetic resonance imaging (MRI) is presented. Features of the technique include measurement of precontrast tumor T(1), rapid temporal sampling, measurement of the arterial input function, and use of a distributed parameter tracer kinetic model. Parameter measurements are compared that were determined using two contrast agents of different molecular weights, gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA; 0.6 kDa) and Gadomer-17 (17 kDa), in 18 spontaneous canine mammary tumors. Measurements of Frho and v(b) corresponded well with literature values, and the mean PSrho measured using Gd-DTPA was a factor of 15 higher than that measured using Gadomer-17. J. Magn. Reson. Imaging 2000;12:991-1003.

Animals↗

Contrast-enhanced MRI for the assessment of myocardial viability after permanent coronary artery occlusion.

Previous studies in a model of ischemia/reperfusion using a constant infusion of Gd-DTPA have shown that distribution volume (lambda) is increased in infarcted myocardial tissue. This study examined this technique in the setting of permanent coronary artery occlusion. Ten beagles underwent permanent occlusion of a coronary artery for 2 days (N = 3), 1 week (N = 4), or 3 weeks (N = 3). Imaging was performed at 2 days and, depending on the length of occlusion, 1 week, 2 weeks, and 3 weeks to follow changes in lambda in vivo. At sacrifice, (201)Tl was injected and the extent of the hyperenhanced region was compared to pathology. lambda was increased in infarcted tissue by 2 days post occlusion and this increase persisted for 3 weeks. At sacrifice, lambda correlated strongly with (201)Tl uptake (r = -0.86 to -0.95, P < 0.05; i.e., lambda increased in infarcted tissue) and the size of the hyperenhanced region was comparable to pathological infarct size (slope 1.006, r = 0.96, P < 0.0001). Thus, beyond 2 days after coronary occlusion, MRI, during a constant infusion of Gd-DTPA, can assess myocardial viability regardless of the success of reperfusion. Magn Reson Med 44:309-316, 2000.

Analysis of Variance↗

Effect of ispaghula husk on the faecal output of bile acids in healthy volunteers.

Faecal bile acids are associated with both colorectal cancer and serum cholesterol levels. We investigate whether dosing with ispaghula husk affects the faecal bile acid weights and concentrations in healthy adults. Sixteen healthy volunteers consumed 7.0 g/day ispaghula husk, containing 5.88 g/day Englyst-determinable dietary fibre, for the middle 8 weeks of a 12-week period. Stool samples were collected, analysed for faecal bile acids and their form and dry weight determined. Correlations between the faecal bile acids, the stool parameters and the dietary intake were tested. Ispaghula husk treatment significantly lowers faecal lithocholic and isolithocholic acids and the weighted ratio of lithocholic acids to deoxycholic acid. These effects revert towards their initial states at the end of the treatment period. These changes in the faecal bile acid profiles indicate a reduction in the hydrophobicity of the bile acids in the enterohepatic circulation.

Adult↗

Primary care workshops can reduce and rationalize antibiotic prescribing.

We describe a controlled study comparing the effects on primary care prescribing in west Gloucestershire, UK, where antibiotic workshops were offered, with those in east Gloucestershire, where microbiology tutorials were given. The year-on-year changes in quantity and costs of antibiotics dispensed following general practice prescriptions were measured. There was no significant difference in the number of antibiotic items prescribed across the county, but the number of prescriptions for broad-spectrum agents (quinolones, cephalosporins and co-amoxiclav) declined by 15.4% in west Gloucestershire, compared with a 6.5% increase in east Gloucestershire (P: = 0.002). Use of narrow-spectrum antibiotics (penicillin V, trimethoprim and nitrofurantoin), whose use was encouraged, did not change in west Gloucestershire practices, but decreased by 12% in east Gloucestershire practices (P: = 0.003). There was increased use of clarithromycin and azithromycin in both groups of practices. Antibiotic workshops held in the primary care setting can rationalize antibiotic prescribing. This can reduce prescribing costs and selection pressure by broad-spectrum antimicrobial agents and, perhaps, go some way to reducing the development of resistance.

Anti-Bacterial Agents↗

Recent trends in physician diagnosed COPD in women and men in the UK.

BACKGROUND: Recent trends in physician diagnosed chronic obstructive pulmonary disease (COPD) in the UK were estimated, with a particular focus on women. METHODS: A retrospective cohort of British patients with COPD was constructed from the General Practice Research Database (GPRD), a large automated database of UK general practice data. Prevalence and all-cause mortality rates by sex, calendar year, and severity of COPD, based on treatment only, were estimated from January 1990 to December 1997. RESULTS: A total of 50 714 incident COPD patients were studied, 23 277 (45.9%) of whom were women. From 1990 to 1997 the annual prevalence rates of physician diagnosed COPD in women rose continuously from 0.80% (95% CI 0.75 to 0.83) to 1.36% (95% CI 1.34 to 1.39), (p for trend <0.01), rising to the rate observed in men in 1990. Increases in the prevalence of COPD were observed in women of all ages; in contrast, a plateau was observed in the prevalence of COPD in men from the mid 1990s. All-cause mortality rates were higher in men than in women (106.8 versus 82.2 per 1000 person-years), with a consistently increased relative risk in men of 1.3 even after controlling for the severity of COPD. Significantly increased mortality rates were also observed in adults aged less than 65 years. The mean age at death was 76.5 years; patients with severe COPD died an average of three years before those with mild disease (p<0.01) and four years before the age and sex matched reference population. CONCLUSIONS: While prevalence rates of COPD in the UK seem to have peaked in men, they are continuing to rise in women. This trend, together with the ageing of the population and the long term cumulative effect of pack-years of smoking in women, is likely to increase the present burden of COPD in the UK.

Aged↗