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Biomedical subjects

R Edwards

Publications and source records attributed to R Edwards.

At least 55 records · Page 3Linked to original sources

Plant glutathione S-transferases: enzymes with multiple functions in sickness and in health.

Glutathione S-transferases (GSTs) are abundant proteins encoded by a highly divergent, ancient gene family. Soluble GSTs form dimers, each subunit of which contains active sites that bind glutathione and hydrophobic ligands. Plant GSTs attach glutathione to electrophilic xenobiotics, which tags them for vacuolar sequestration. The role of GSTs in metabolism is unclear, although their complex regulation by environmental stimuli implies that they have important protective functions. Recent studies show that GSTs catalyse glutathione-depend-ent isomerizations and the reduction of toxic organic hydroperoxides. GSTs might also have non-catalytic roles as carriers for phytochemicals.

Catalysis↗

Identification of three triterpenoids in almond hulls.

Three triterpenoids, betulinic acid, oleanolic acid, and ursolic acid, were isolated as their methyl esters (treatment with diazomethane) from diethyl ether extracts of almond hulls (Nonpareil variety) using flash chromatography and preparative high-performance liquid chromatography. The triterpenoids, which comprised approximately 1% of the hulls, were characterized using chromatographic and spectroscopic methods. These studies demonstrate that almond hulls are a rich source of these triterpenoids, which have reported anti-inflammatory, anti-HIV, and anti-cancer activities.

Chromatography, Gas↗

Investigation of executive function change following anterior temporal lobectomy: selective normalization of verbal fluency.

The nociferous cortex hypothesis predicts that electrophysiological normalization to distal extratemporal brain regions following anterior temporal lobectomy (ATL) will result in improvements in executive functioning. The present study examined the effects of seizure laterality and seizure control on executive function change. The authors administered the Wisconsin Card Sorting Test (WCST), Trails B, and the Controlled Oral Word Association Test to 174 temporal lobe epilepsy patients who underwent ATL. No significant changes were found on the WCST or Trails B tests, regardless of surgery side or seizure-free status. However, verbal fluency significantly improved in seizure-free patients. Findings were consistent with the nociferous cortex hypothesis suggesting selective executive function improvement following ATL. These findings are discussed in terms of recent research demonstrating extrahippocampal metabolic normalization following surgery.

Adolescent↗

Human area V5 and motion in the ipsilateral visual field.

We have studied area V5 of the human brain with visually-evoked potential (VEP) and functional magnetic resonance imaging (fMRI) methods, using hemifield motion stimuli. Our results confirmed the presence of an ipsilateral field representation in V5 and found: (i) a delay in the ipsilateral response in V5, irrespective of the hemifield stimulated; (ii) a longer ipsilateral delay for left hemifield than for right hemifield stimulation; and (iii) in a patient with a section of the splenium, an absent ipsilateral response for right but not left hemifield stimulation. Together with neurophysiological and anatomical evidence in the monkey, our non-invasive spatial and temporal imaging studies in man reveal that ipsilateral V5 is activated by motion signals transferred from contralateral V5. The asymmetry of ipsilateral delay in normal subjects and the asymmetrical loss of ipsilateral response following splenial section imply that signals related to visual motion are transferred from one V5 to the other through two segregated pathways.

Adult↗

Lung cancer treatment waiting times and tumour growth.

We report a single-centre prospective audit of 29 lung cancer patients who were awaiting radical (potentially curative) radiotherapy. This was the total number assessed as suitable for radical treatment by one consultant during 1999. At the time of assessment they had been newly diagnosed and staged with a computed tomographic (CT) scan of chest. They had a subsequent CT scan prior to starting treatment for the purpose of planning the radiation fields. We have now measured tumour size on the diagnostic scans and compared this with the size on the planning scans. We have documented the delay between diagnostic and planning CT scanning and the total time between first hospital visit and starting treatment. Two patients had progression of symptoms while on the waiting list, making them unfit for radical treatment, and another four had tumour progression on planning CT such that the tumour volume was too large for radical treatment. Therefore, 21% of potentially curable patients became incurable on the waiting list. The delay between diagnostic and planning CT scans ranged from 18 to 131 days (median 54), with increases in the cross-sectional tumour size over that period ranging zero to 373%. The delay between the first hospital visit and starting treatment was 35-187 days (median 94); between the date of the radiotherapy request and the starting date for treatment it was 23-61 days (median 44). Limited access to specialists is the reason most often advanced for the poor performance of the UK in treating lung cancer. This study demonstrates that, even for the select minority of patients who have specialist referral and are deemed suitable for potentially curative treatment, the outcome is prejudiced by waiting times that allow tumour progression.

Aged↗

Elevated tumour marker CA19-9: clinical interpretation and influence of obstructive jaundice.

AIMS: The tumour marker CA19-9 has been promoted as a reliable test for the detection of pancreatobiliary malignancy, yet its diagnostic role remains poorly defined. In this study the clinical interpretation of a raised serum CA19-9 level has been evaluated, with particular reference to obstructive jaundice. METHODS: One hundred and sixty-four patients with a CA19-9 level above 33 U/ml were studied. Serum CA19-9 was compared with clinical diagnosis and correlated with serum bilirubin level. In a subgroup of jaundiced patients (16 benign and 15 malignant cases), follow-up CA19-9 levels were determined 2 weeks after biliary drainage. RESULTS: The median CA19-9 level was lower in benign cases (102 (IQR 50-264) U/ml) than those with pancreatobiliary tumours (910 (IQR 263-6170) U/ml; P<0.01), although the overlap was substantial. In benign jaundiced cases, a positive correlation was observed between bilirubin and CA19-9 elevation (R=0.41, P<0.01). Relief of jaundice was associated with a fall in CA19-9 level in all benign cases and in nine of the 15 with malignancy. CONCLUSION: Confident discrimination between benign and malignant disease could not be made on the basis of a solitary elevated CA19-9 measurement. Hyperbilirubinaemia was associated with a further deterioration in specificity and caution is warranted when interpreting the results in jaundiced patients. Overall, only one half of patients with an elevated CA19-9 level ultimately proved to harbour a malignancy.

Adult↗

Expression of the carbapenemase gene (cfiA) in Bacteroides fragilis.

Bacteroides fragilis strains were studied to examine carbapenemase gene (cfiA) expression and insertion sequence (IS) element promoters. High-level resistance was associated with high meropenemase activity and IS elements upstream of cfiA. Sequencing revealed two element types; IS1187 and elements related to IS942 and IS1170. The latter was implicated in the conversion to carbapenem resistance in a cfiA-positive isolate during imipenem therapy. Two strains showing low-level resistance, and strains susceptible to meropenem, did not possess IS elements upstream of cfiA. The prevalence in Nottingham of clinical isolates of B. fragilis with cfiA and efficient IS element promoters was low (0.6%).

Bacterial Proteins↗

Sex-specific effects of pain-related anxiety on adjustment to chronic pain.

OBJECTIVE: Considerable research indicates that both high levels of anxiety and female sex are associated with increased sensitivity to experimental pain and greater experience of clinical pain. In general, however, previous research has not investigated the joint effects of sex and anxiety on pain responses. A single previous laboratory-based study indicated that anxiety was inversely related to pain thresholds among men but not among women. The present study examined the relation between pain-related anxiety and adjustment to chronic pain in a sex-dependent manner. DESIGN AND SETTING: A total of 215 (114 women, 101 men) chronic pain patients referred to a multidisciplinary treatment center completed questionnaires assessing anxiety and adjustment to chronic pain. RESULTS: Results generally supported the previous laboratory-based finding indicating that an inverse relation between anxiety and adjustment to chronic pain was present only among male patients. Although male patients with high pain-related anxiety reported greater pain severity, greater interference of pain, and lower levels of daily activity than male patients with low anxiety, this effect was not present among female patients. Moreover, the effects of pain-related anxiety on adjustment to chronic pain were not attributable to either hypervigilance or use of passive coping strategies. Potential explanations and implications for the present findings are discussed.

Activities of Daily Living↗

Using time domain characteristics to discriminate physiologic and parkinsonian tremors.

Tremor amplitude and frequency do not always clearly differentiate subjects with particular pathologies from control subjects or from subjects with other pathologies, especially in early stages of a disease. For patients with early stages of Parkinson's disease (PD) the discriminative power of amplitude was compared with that of other time domain characteristics of tremor recordings that are probably not evident clinically. Postural tremor with and without visual feedback and rest tremor were recorded in both hands of a group of patients with Parkinson's disease (n = 21) and a group of healthy control subjects (n = 30) using displacement lasers. Velocity and acceleration data were derived from displacement data. Twelve time domain characteristics were calculated on each recording and the discriminating power of each was evaluated using the worse hand in each case. Postural tremor with no visual feedback separates the two groups of subjects most efficiently, especially in velocity and acceleration. Tremor in Parkinson's disease (in comparison to normal physiologic tremor) has a specific morphology, has a distinctive histogram, is more periodic, and contains indications of nonlinearity in the underlying dynamics. There may also be greater difference in amplitude between the two hands and time asymmetry in tremor of patients with PD. A series of finger flexions seems to enhance normal tremor but not tremor in PD and may thus aid in discrimination. Discrimination of tremor attributable to PD from normal physiologic tremor can be enhanced by measuring time domain characteristics subtler than amplitude, particularly when amplitude itself is not large. Tremor measurement should not be limited to acceleration data because some information is more visible in other variables.

Aged↗

Hypertension prevalence and care in an urban and rural area of Tanzania.

OBJECTIVE: To describe the prevalence, detection, treatment and control of hypertension in an urban and rural area of Tanzania. DESIGN: Two linked cross-sectional population-based surveys. SETTING: A middle-income urban district of Dar es Salaam (Ilala) and a village in the relatively prosperous rural area of Kilimanjaro (Shari). PARTICIPANTS: Seven hundred and seventy adults (> 15 years) in Ilala and 928 adults in Shari were studied. RESULTS: Hypertension prevalence (blood pressure > or = 140 and/or 90 mmHg, or known hypertensives receiving anti-hypertensive treatment) was 30% (95% confidence interval, 25.1-34.9%) in men and 28.6% (24.3-32.9%) in women in Ilala, and 32.2% (27.7-36.7%) in men and 31.5% (27.8-35.2%) in women in Shari. Age-standardized hypertension (to the New World Population) prevalence was 37.3% (32.2-42.5%) among men and 39.1% (34.2-44.0%) in women in Ilala, and 26.3% (22.4-30.4%) in men and 27.4% (24A-30.4%) in women in Shari. In both areas, just under 20% of hypertensive subjects were aware of their diagnosis, approximately 10% reported receiving treatment and less than 1% were controlled (blood pressure < 140/90 mmHg). Hypertensive subjects were older, had greater body mass indices and waist: hip ratios, and had more risk factors for hypertension and its complications (smoking, heavy alcohol consumption, physical inactivity, obesity and diabetes) than non-hypertensives. CONCLUSIONS: There is a high prevalence of hypertension in rural and urban areas of Tanzania, with low levels of detection, treatment and control. This demonstrates the need for cost-effective strategies for primary prevention, detection and treatment of hypertension and the growing public health challenge of non-communicable diseases in Sub-Saharan Africa.

Adolescent↗

Predictors of attendance in the United Kingdom flexible sigmoidoscopy screening trial.

OBJECTIVE: To investigate predictors of attendance in the United Kingdom flexible sigmoidoscopy screening trial. DESIGN: Prospective design in which participants completed a postal questionnaire before being sent their invitation for screening. SETTING: Welwyn Garden City and Leicester, United Kingdom. PARTICIPANTS: A total of 2758 patients aged 55 to 64, registered with general practices in the two centres, who (a) expressed interest in having the screening test, (b) completed a postal questionnaire, and (c) were subsequently invited for screening. MAIN RESULTS: The attendance rate among questionnaire responders was 76.1%. Multiple logistic regression analysis yielded a final model that included nine independent predictors of attendance. Patients with the following characteristics were more likely to attend: men; home owners; non-smokers; those who had regular check ups at the dentist; those with better subjective health; those who minded less about having medical tests; those who said they would definitely rather than probably take up the offer of sigmoidoscopy screening; and those who perceived less barriers and more benefits to having the test. CONCLUSIONS: The findings are broadly consistent with previous studies of screening participation, although subjective health emerged as an important predictor in this study. There was no evidence for "reverse targeting": attenders were not at lower (or higher) risk for colorectal cancer compared with non-attenders. The findings relating to attitudes and beliefs could be used in efforts to improve attendance, for example by developing information leaflets that address barriers to screening. Other findings could be used to target interventions to subgroups that have relatively low rates of screening participation.

Age Factors↗

Measurement of glycated haemoglobin in whole blood by a novel fluorescence quenching assay.

We describe a method for the specific measurement of glycated Hb (GHb) by fluorescence quenching. Whole blood is added to lysing solution, then the lysate is mixed with eosin-boronic acid solution and reacted for at least 5 min at room temperature. The quenching of the fluorescence of the eosin-boronic acid solution is proportional to the concentration of GHb present. Total Hb concentration was measured by absorbance and the GHb expressed as a percentage of the total Hb. Comparison with a commercial high-performance liquid chromatography (HPLC) system for HbA1c showed: %GHb=1.30 (SD 0.04) %HbA1c + 1.36 (SD 0.30), S(y/x) 0.803, n=95, r=0.965 (SD=standard deviation). Intra-assay coefficients of variation were <2.5% (for GHb concentrations in the range 6-20%) and inter-assay coefficients of variation were <4.1% (10 assays on six samples with GHb concentrations in the range 6-20%). Linearity of response was demonstrated by dilution. The effect of adding exogenous glucose, bilirubin and triglycerides was tested on samples with low, medium and high GHb concentrations. No significant interference was found. Variation of haematocrit over the range 0.4-0.6 also had no significant effect on percentage GHb. Preliminary results with samples containing variant Hb (HbAS and HbAC) indicated good agreement with HPLC for these samples also.

Boronic Acids↗

A reliable non-separation fluorescence quenching assay for total glycated serum protein: a simple alternative to nitroblue tetrazolium reduction.

A simple non-separation assay for the measurement of total glycated serum protein is described. It was found that the fluorescence intensity of a solution of a fluorescein-boronic acid derivative was quenched in proportion to the amount of serum added. This led to the development of an assay in which 10 microL of serum is added to 4 mL of a solution of the fluorescein-boronic acid derivative and the fluorescence intensity is measured after 15 min. The results, as measured by drop in fluorescence intensity, calibrated by a single standard, were compared with the results for nitroblue tetrazolium (NBT) reduction of fructosamine and showed good correlation (r=0.936, n=114). The intra-assay precision (seven samples each measured 10 times) was less than 2.1% (concentration range 190-660 micromol/L); inter-assay precision for seven samples in 10 assays was less than 2.5% (over the same concentration range). Dilution of serum that had a high concentration of total glycated protein showed the assay to be linear. Serum samples (with low, medium and high total glycated protein concentrations) showed less than 2.1% difference from base results with added glucose (up to 60 mmol/L), less than 9.7% difference with added bilirubin (up to 250 micromol/L) and less than 6.9% with added triglycerides (up to 50 mmol/L). Addition of haemoglobin (up to 0.9 g/dL) with high glycation (11.7% HbA1c) to plasma (298 micromol/L total glycated protein) showed less than 10% difference from the base result. Assays performed over a range of temperatures (12-34 degrees C) showed no significant differences in the results. The assay gives similar results to the currently used NTB method but with significantly less susceptibility to interferences. As such the method should be a useful aid in the management of diabetes.

Blood Proteins↗

Physiological tremor: does handedness make a difference?

The purpose of this study was to quantify with precision the characteristics of normal physiological tremor in the dominant and nondominant hand of a group of right-handed females. Twenty-two right-handed females (aged 20 to 40) gave informed consent to participate. Manual dominance determined with a questionnaire had to be equal to, or above 90%, for subjects to be accepted in the study. While the subjects kept their eyes closed, tremor was recorded simultaneously in the two extended index fingers during 40 s. Preceding the recording of postural tremor there was a period during which the subjects were asked to relax (control condition); to exert a pressure with the two index fingers on two strain gauges (static condition); or to press on and off with both index fingers on two strain gauges (dynamic condition). Each condition was recorded twice with two helium neon velocity lasers. This procedure was repeated after permutation of the lasers, thus a total of twelve sweeps of data were recorded. Seven parameters were used to analyze the tremor signal including measures of harmonicity, median frequency, proportional power in the 7-12 Hz range, amplitude, waveform morphology, entropy, and nonlinearity. Significant differences between hands were found in three parameters (median frequency, power in 7-12 Hz and entropy) but not in tremor amplitude (RMS). In addition, significant differences were found in five out of seven characteristics between conditions. These results suggest that neuromotor activity preceding the recording of tremor has a significant influence on tremor characteristics and that some of these characteristics are significantly different between the right and left hand in right-handed females.

Adult↗