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L Walker

Publications and source records attributed to L Walker.

At least 19 recordsLinked to original sources
PubMed2006

Surveillance for Wilms tumour in at-risk children: pragmatic recommendations for best practice.

BACKGROUND: Most Wilms tumours occur in otherwise healthy children, but a small proportion occur in children with genetic syndromes associated with increased risks of Wilms tumour. Surveillance for Wilms tumour has become widespread, despite a lack of clarity about which children are at increased risk of these tumours and limited evidence of the efficacy of screening or guidance as to how screening should be implemented. METHODS: The available literature was reviewed. RESULTS: The potential risks and benefits of Wilms tumour surveillance are finely balanced and there is no clear evidence that screening reduces mortality or morbidity. Prospective evidence-based data on the efficacy of Wilms tumour screening would be difficult and costly to generate and are unlikely to become available in the foreseeable future. CONCLUSIONS: The following pragmatic recommendations have been formulated for Wilms tumour surveillance in children at risk, based on our review: (1) Surveillance should be offered to children at >5% risk of Wilms tumour. (2) Surveillance should only be offered after review by a clinical geneticist. (3) Surveillance should be carried out by renal ultrasonography every 3-4 months. (4) Surveillance should continue until 5 years of age in all conditions except Beckwith-Wiedemann syndrome, Simpson-Golabi-Behmel syndrome and some familial Wilms tumour pedigrees where it should continue until 7 years. (5) Surveillance can be undertaken at a local centre, but should be carried out by someone with experience in paediatric ultrasonography. (6) Screen-detected lesions should be managed at a specialist centre.

Chromosome Disorders↗
PubMed2006

A prospective study of neurofibromatosis type 1 cancer incidence in the UK.

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition affecting around one in 3000 live births. The manifestations of this condition are extremely variable, even within families, and genetic counselling is consequently difficult with regard to prognosis. Individuals with NF1 are acknowledged to be at increased risk of malignancy. Several studies have previously attempted to quantify this risk, but have involved relatively small study populations. We present prospective data from 448 individuals with NF1 with a total of 5705 years of patient follow-up. These data have been collected via the UK NF1 association for patients. Demographic information on the affected individuals was cross-referenced with UK cancer registry data by the UK Office of National Statistics. The overall risk of cancer was 2.7 times higher in this cohort of NF1 patients than in the general population (95% confidence interval (CI) 1.9-3.7). The cumulative risk of a malignancy by age 50 years was 20% (95% CI 14-29%); beyond this age, the risk of cancer was not significantly elevated (P=0.27). The most frequent types of cancer were connective tissue (14% risk by age 70, 95% CI 7.8-24%) and brain tumours (7.9, 95% CI 3.9-16%). There was no statistically significant excess of cancers at other sites (P=0.22).

Adolescent↗
PubMed2006

Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour.

Wilms tumour has been reported in association with over 50 different clinical conditions and several abnormal constitutional karyotypes. Conclusive evidence of an increased risk of Wilms tumour exists for only a minority of these conditions, including WT1 associated syndromes, familial Wilms tumour, and certain overgrowth conditions such as Beckwith-Wiedemann syndrome. In many reported conditions the rare co-occurrence of Wilms tumour is probably due to chance. However, for several conditions the available evidence cannot either confirm or exclude an increased risk, usually because of the rarity of the syndrome. In addition, emerging evidence suggests that an increased risk of Wilms tumour occurs only in a subset of individuals for some syndromes. The complex clinical and molecular heterogeneity of disorders associated with Wilms tumour, together with the apparent absence of functional links between most of the known predisposition genes, suggests that abrogation of a variety of pathways can promote Wilms tumorigenesis.

Chromosome Aberrations↗
PubMed2006

Measuring the impact of intimate partner violence on the health of women in Victoria, Australia.

OBJECTIVE: Using burden of disease methodology, estimate the health risks of intimate partner violence (IPV) among women in Victoria, Australia. METHODS: We calculated population attributable fractions (from survey data on the prevalence of IPV and the relative risks of associated health problems in Australia) and determined health outcomes by applying them to disability-adjusted life year estimates for the relevant disease and injury categories for Victoria, Australia for 2001. FINDINGS: For women of all ages IPV accounted for 2.9% (95% uncertainty interval 2.4-3.4%) of the total disease and injury burden. Among women 18-44 years of age, IPV was associated with 7.9% (95% uncertainty interval 6.4-9.5%) of the overall disease burden and was a larger risk to health than risk factors traditionally included in burden of disease studies, such as raised blood pressure, tobacco use and increased body weight. Poor mental health contributed 73% and substance abuse 22% to the disease burden attributed to IPV. CONCLUSION: Our findings suggest that IPV constitutes a significant risk to women's health. Mental health policy-makers and health workers treating common mental health problems need to be aware that IPV is an important risk factor. Future research should concentrate on evaluating effective interventions to prevent women being exposed to violence, and identifying the most appropriate mental health care for victims to reduce short- and long-term disability.

Adolescent↗
PubMed2005

Redefining the coronary care unit: an observational study of patients admitted to hospital in England and Wales in 2003.

BACKGROUND: Coronary care units were developed in the 1960s as specially equipped and staffed areas where patients with acute myocardial infarction could be monitored and offered rapid resuscitation from life-threatening arrhythmias. Awareness of the morbidity and mortality of the wider spectrum of acute coronary ischaemia was unrecognized at that time. AIM: To examine the relative frequencies with which thrombolytic treatment and resuscitation from cardiac arrest are provided for patients with myocardial infarction in cardiac care units (CCUs), emergency departments (EDs) and other medical wards. DESIGN: Observational study. METHODS: We analysed records from the National Audit of Myocardial Infarction Project (MINAP) for 61 688 patients admitted to 230 acute hospitals in England and Wales during 2003, and who received a final diagnosis of myocardial infarction, for locations of initiation of thrombolytic therapy and of first cardiac arrest within hospital. RESULTS: Overall, 84% of 27 881 patients with ST-segment-elevation infarction, but only 42% of 30 382 patients with non-ST-elevation infarction, were admitted to a CCU. Of those receiving thrombolytic treatment for ST-elevation infarction, 68.3% of 21 595 did so in the ED. Within the first 4 h after arrival, the majority of episodes of cardiac arrest occurred in the ED: 709 (57%) vs. 488 (39%) in CCU, and 49 (4%) in medical wards. DISCUSSION: The traditional role of the CCU in providing early resuscitation and thrombolytic treatment for patients with ST elevation infarction has largely been devolved to the ED. The role of the CCU should be re-evaluated, and the service re-designed to provide specialist care for all presentations of acute coronary syndrome.

Aged↗
PubMed2005

Associations between BMI, social strata and the estimated energy content of foods.

OBJECTIVE: Many studies have shown that the prevalence of obesity is greater in lower social classes. The reasons for this effect however are unclear. Since there is also a link between education and social class, and an association between education and prevalence of obesity, one hypothesis is that lack of education about energy contents of foods may contribute to the effects of social class on obesity. SUBJECTS: We tested the hypothesis that knowledge of food energy contents is associated with differences in body mass index (BMI) in a sample of 346 people of both genders, aged between 18 and 45 y, of variable body mass index and drawn from different social strata. RESULTS: Estimates of food energy contents were on average well correlated with the actual energy contents, but individual estimates were very poor in all subpopulations of this sample. We found that subjects of different BMIs did not differentially estimate the energy contents of foods high in carbohydrate, but low in fat and protein (fruit and bread). However, foods that contained high fat contents, independent of the other macronutrients present, were generally perceived to have significantly lower energy contents by obese people than nonobese subjects (although this was not observed for all high-fat foods). Overall, this difference interacted with social class, such that the difference between the BMI groups was exaggerated in the lower social stratum but abolished in the higher social class. Binary logistic regressions revealed that the probability of being obese (BMI>30 kg/m2) in the lower social class group was significantly negatively associated with the estimated food energy content of most high-fat foods. Such an association was not found in the higher social class group. In the lower social class group, overall food knowledge appeared superior in the leaner subject group (BMI<30 kg/m2), but obese subjects were actually better at estimating the energy contents of snacks and alcoholic beverages. The leaner group significantly overestimated the energy contents of these items. CONCLUSION: Differences between individuals in estimates of food energy contents may contribute to the development of obesity in lower social strata. Whether this is driven by a protective effect in lean subjects of overestimating the energy contents of certain foods (snacks and alcoholic beverages) or a susceptibility in the obese because they underestimate the energy contents of other foods is not certain. Knowing which of these alternatives is true is important and may help design public health education programmes directed at these people to help alleviate the obesity epidemic.

Adolescent↗
PubMed2005

Global perspectives on animal welfare: Asia, the Far East, and Oceania.

In Asia and the Far East, livestock undergo major suffering due to malnutrition, overloading, and ill-treatment. At slaughter animals are handled roughly and watch other animals being killed; stunning is not practised. Cruelty to other animals such as elephants, horses, donkeys, bears, dogs, and circus animals has largely been prevented through the efforts of animal welfare organisations. Governments have taken initiatives to establish Animal Welfare Boards and enact laws for the prevention of cruelty to animals, but their efforts are far too limited to be of any significance and financial constraints and lack of personnel inhibit the implementation of the laws that do exist. In New Zealand and Australia, legislation and strong consultation procedures at governmental and community level strive to regulate and improve the welfare of animals in all spheres, but in other Oceanic countries there is a need for both an update in, or establishment of, legislation covering animal welfare. Limited progress has been made due to the status of the Veterinary Services and a lack of resources. Although some public and educational awareness programmes are carried out, increasing exposure to international media and attitudes of visiting tourists suggest that further awareness work needs to be undertaken. To address the problems of animal welfare in developing countries, it would be inappropriate to adopt the international standards that are implemented in the developed countries. Each developing country should evolve its own standards based on its own individual priorities.

Animal Diseases↗
PubMed2004

Pharmacological activities of some Argyranthemum species growing in the Canary Islands.

Methanolic extracts of eight subspecies of genus Argyranthemum were evaluated against brine shrimps, human cancer cell lines, malarial parasites and microorganisms under in vitro conditions. In the shrimp assay, samples of A. adauctum ssp. adauctum, A. adauctum ssp. erythrocarpon and A. frutetescens ssp. succulentum were active with ED50 values in the range of around 300 to 360 microg/ml. In the Caco-2, HepG2 and MCF-7 cell lines, the samples A. adauctum ssp. jacobaeifolium and A. adauctum ssp. palmensis were active with LC50 values ranging between 80-90 microg/ml. The secondary assay results of antimalarial activity of samples, A. adauctum ssp. adauctum, A. adauctum ssp. dugourii, A. adauctum ssp. erythrocarpon and A. adauctum ssp. jacobaeifolium have IC50 values <50 microg/ml. The samples demonstrated broad specific antimicrobial activity against five different microorganisms.

Animals↗
PubMed2004

Accelerated accumulation of N- and C-terminal beta APP fragments and delayed recovery of microtubule-associated protein 1B expression following stroke in aged rats.

The age-related decline in plasticity of the brain may be one factor underlying poor functional recovery after stroke. In the present work we tested the hypothesis that the attenuation of neural plasticity in old age could be the result of an altered temporal relationship between factors promoting brain plasticity [microtubule-associated protein 1B (MAP1B)] and neurotoxic factors such as C-terminal betaAPP. Focal cerebral ischemia was produced by reversible occlusion of the right middle cerebral artery in 3- and 20-month-old male Sprague-Dawley rats. The functional outcome was assessed in neurobehavioral tests at 3, 7, 14 and 28 days after surgery. At the indicated timepoints, brains were removed and immunostained for C- and N-terminal betaAPP and MAP1B. At 2 weeks poststroke, we found an age-related increase in the amount of the C-terminal fragment of betaAPP in the peri-infarcted area and the infarct core as well as an early, vigorous incorporation of N-terminal betaAPP into the developing astroglial scar. The recovery of the plasticity-associated protein MAP1B following stroke was delayed in both age groups and became prominent between days 14 and 28. As aged rats showed diminished functional recovery compared with young rats, these results suggest that the accumulation of C-terminal betaAPP, together with the early incorporation of N-terminal betaAPP into the glial scar, may over-ride the beneficial role of plasticity factors such as MAP1B.

Aging↗
PubMed2004

Improving care for patients with acute coronary syndromes: initial results from the National Audit of Myocardial Infarction Project (MINAP).

OBJECTIVE: To describe the improvements in care that have followed the introduction of an electronic data entry and analysis system providing contemporary feedback on the management of acute coronary syndromes in 230 hospitals in England and Wales. DESIGN: Observational study METHODS: A secure electronic system was used to transfer encrypted data on patients with acute coronary syndromes from collaborating hospitals to central servers for analysis. Immediate online data entry to the central servers by hospitals allowed contemporary analyses of performance and immediate comparison with the national aggregate performance. RESULTS: The records of 156 902 patients receiving a final diagnosis of acute coronary syndrome during three years between October 2000 and September 2003 were analysed. Of 69 113 patients with ST segment elevation infarction, 75.4% received thrombolytic treatment. Between the first and last years of the study the median interval from hospital arrival to treatment fell for eligible patients from 38 (interquartile range 22-58) to 20 (interquartile range 14-28) minutes. By mid 2003 77.6% were receiving thrombolytic treatment within 30 minutes of arrival. The proportion treated within two hours of onset of symptoms increased from 32.5% to 40.3% (a difference of 7.8 percentage points, p < 0.0001). The use of secondary prevention medication for acute coronary syndromes increased over this period: angiotensin converting enzyme inhibitors, 62.4% to 72.4%; beta blockers, 76.3% to 82.6%; statins, 69.6% to 83.8%; and aspirin, 89.3% to 90.2%. CONCLUSION: The provision of contemporary online performance analyses has underpinned substantial improvement in the care of patients with acute coronary syndromes.

Adrenergic beta-Antagonists↗
PubMed2003

mRNA and protein expression of dog liver cytochromes P450 in relation to the metabolism of human CYP2C substrates.

1. Interpretation of novel drug exposure and toxicology data from the dog is tempered by our limited molecular and functional knowledge of dog cytochromes P450 (CYPs). The aim was to study the mRNA and protein expression of hepatic dog CYPs in relation to the metabolism of substrates of human CYP, particularly those of the CYP2C subfamily. 2. The rate of 7-hydroxylation of S-warfarin (CYP2C9 in humans) by dog liver microsomes (mean +/- SD from 12 (six male and six female) dogs = 10.8 +/- 1.9 fmol mg(-1) protein min(-1)) was 1.5-2 orders of magnitude lower than that in humans. 3. The rate of 4'-hydroxylation of S-mephenytoin, catalysed in humans by CYP2C19, was also low in dog liver (4.6 +/-1.5 pmol mg(-1) protein min(-1)) compared with human liver. In contrast, the rate of 4'-hydroxylation of the R-enantiomer of mephenytoin by dog liver was much higher. The kinetics of this reaction (range of K(m) or K(0.5) 15-22 micro M, V(max) 35-59 pmol mg(-1) protein min(-1), n = 4 livers) were consistent with the involvement of a single enzyme. 4. In contrast to our findings for S-mephenytoin, dog liver microsomes 5'-hydroxylated omeprazole (also catalysed by CYP2C19 in humans) at considerably higher rates (range of K(m) 42-64 micro M, V(max) 22-46 pmol mg(-1) protein min(-1), n = 4 livers). 5. For all the substrates except omeprazole, a sex difference in their metabolism was observed in the dog (dextromethorphan N-demethylation: female range = 0.7-0.9, male = 0.4-0.8 nmol mg(-1) protein min(-1) (p < 0.02); S-warfarin 7-hydroxylation: female = 9-15.5, male = 8-12 fmol mg(-1) protein min(-1) (p < 0.02); R-mephenytoin 4'-hydroxylation: female = 16-35, male = 11.5-19 pmol mg(-1) protein min(-1) (p < 0.01); omeprazole 5'-hydroxylation: female = 15-20, male 13-22 pmol mg(-1) protein min(-1) (p < 0.2)). 6. All dog livers expressed mRNA and CYP3A12, CYP2B11, CYP2C21 proteins, with no sex differences being found. Expression of CYP2C41 mRNA was undetectable in the livers of six of 11 dogs. 7. Correlation analysis suggested that CYP2B11 catalyses the N-demethylation of dextromethorphan (mediated in humans by CYP3A) and the 4'-hydroxylation of mephenytoin (mediated in humans by CYP2C19) in the dog, and that this enzyme and CYP3A12 contribute to S-warfarin 7-hydroxylation (mediated in humans by CYP2C9). 8. In conclusion, we have identified a distinct pattern of hepatic expression of the CYP2C41 gene in the Alderley Park beagle dog. Furthermore, marked differences in the metabolism of human CYP2C substrates were observed in this dog strain compared with humans with respect to rate of reaction, stereoselectivity and CYP enzyme selectivity.

Algorithms↗
PubMed2003

Evaluation of magnetic resonance myelography in the investigation of cervical spondylotic radiculopathy.

The objective of this study was to prospectively evaluate the accuracy of MR myelography for the demonstration of foraminal nerve root impingement in cervical spondylotic radiculopathy. 40 patients with cervical spondylotic radiculopathy were imaged with conventional MRI and with MR myelography. The diagnostic accuracy of these imaging strategies for the demonstration of exit foraminal stenosis was calculated relative to a gold standard of the combination of conventional MRI and MR myelography. Conventional MRI had a sensitivity of 88.9%, specificity of 99.1%, and diagnostic accuracy of 94.5% for the demonstration of exit foraminal disease (p<0.001). MR myelography alone had a sensitivity of 84.4%, a specificity of 90.1%, and diagnostic accuracy of 88% (p<0.001). However, the addition of MR myelography increased the diagnostic yield of the MR examination for the detection of foraminal stenotic disease. MR myelography is a useful adjunct to conventional MRI in the investigation of cervical spondylotic radiculopathy.

Adult↗
PubMed2002

Assessment of vessel wall thickness in carotid atherosclerosis using spiral CT angiography.

OBJECTIVES: the purpose of this study was to evaluate the amount of vessel wall thickening in the internal and common carotid arteries in patients undergoing spiral CT angiography for the investigation of significant atherosclerotic disease. MATERIALS AND METHODS: forty-five carotid systems in patients with a 70% or greater stenosis (according to carotid duplex) were imaged with CT spiral angiography using a standardised protocol. The vessel wall thickness of the distal common and mid internal carotid artery was measured using axial CT sections. RESULTS: vessel wall thickness was greater and more variable within the common carotid artery than within the internal carotid artery. The mean proportion of total vessel diameter constituted by vessel wall thickness was significantly greater in the common carotid artery as compared to the internal carotid artery: 28+/-12% (SD) vs 15+/-6%, respectively (p < 0.001). CONCLUSIONS: significant and extended wall thickening is commonly present in the internal and common carotid arteries of patients with atherosclerotic disease, but the internal carotid artery is significantly less affected than the common carotid artery. These observations question the validity of using the common carotid artery as a reference vessel for angiographic stenosis measurements.

Adult↗
PubMed2001

Hemoglobin H (Hb H) disease in Canada: molecular diagnosis and review of 116 cases.

Over the past decade, we have characterized at the DNA level a total of 116 hemoglobin H (Hb H) disease patients living in Canada. The majority of patients were of southeast Asian descent (Chinese, Filipino, Laotian, Vietnamese), with a small number being of Mediterranean, Middle Eastern or East Indian background. A total of 15 distinct genotypes were detected, all but one being compound heterozygotes for a two-gene cis deletion and a single-gene deletion (-alpha/-) or a non-deletion mutation of the alpha2-globin gene (alpha(T) alpha/-). Seven different two-gene cis deletions were encountered, along with nine single-gene deletions and point mutations. The wide range of mutations associated with Hb H disease in Canada is a reflection of the population heterogeneity. The diagnosis of Hb H disease at the molecular level is important with respect to genetic counseling and the identification of families at risk for having pregnancies affected with Hb Bart's hydrops fetalis syndrome and/or Hb H disease. Six of the Hb H disease patients in our cohort had spouses who carried single-gene deletions, making these couples at risk for having children with Hb H disease. More important, seven patients had partners who carried two-gene cis deletions. These couples are at reproductive risk for both Hb Bart's hydrops fetalis syndrome and Hb H disease.

Adolescent↗
PubMed2001

Vascular expression of Notch pathway receptors and ligands is restricted to arterial vessels.

Mice with targeted mutations in genes required for Notch signal transduction die during embryogenesis, displaying overt signs of hemorrhage due to defects in their vascular development. Surprisingly, directed expression of a constitutively active form of Notch4 within mouse endothelial cells produces a similar vascular embryonic lethality. Moreover, patients with mutations in Notch3 exhibit the cerebral vascular disorder, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). These findings underscore the importance of Notch signaling in vascular development; however, they do not identify the specific functional defect. Here, we report that Notch1, Notch3, Notch4, Delta4, Jagged1 and Jagged2 are all expressed in arteries, but are not expressed by veins. These findings identify an aspect of Notch signaling that could contribute to the mechanism by which this pathway modulates vascular morphogenesis.

Animals↗
PubMed2001

Sphygmomanometers in use in general practice: an overlooked aspect of quality in patient care.

OBJECTIVES: To assess the condition, accuracy and safety of mercury and anaeroid sphygmomanometers in use in general practice and to pilot a scheme for sphygmomanometer maintenance within the district. DESIGN: Instruments were checked on site according to set protocols which related to established guidelines and standards and data were entered into a specially designed database. Mercury sphygmomanometers were removed to the laboratory for servicing. Practices received written feedback on the condition of each instrument checked, repairs undertaken and advice, where necessary, for further work required. Participant views on the scheme were sought. MATERIALS AND METHODS: A total of 472 instruments (75.4% mercury) located in 86 general practices (87.8% of practices participated) in a health district in the West Midlands. Instruments were checked against 28 (mercury) and 25 (anaeroid) quality standards and (for mercury instruments) against British Hypertension Society guidelines. RESULTS: 69.1% of mercury and 95.7% of anaeroid instruments checked, had no service records. Of the remainder, only 29 mercury (8.1%) and one anaeroid (0.9%) had a record of a check or service within the previous 12 months. None of the instruments met all of the relevant quality standards and 14 (3.9%) mercury and seven (6.1%) anaeroid instruments met less than half. A large proportion of mercury sphygmomanometers tested had defects likely to affect recommended measurement technique. Only two-thirds were accurate at all pressure levels tested. Only 38.8% of anaeroid instruments were accurate at all test pressure levels. CONCLUSIONS: The level of defects noted could have an impact on diagnosis and monitoring of hypertension.

Equipment Safety↗
PubMed2001

Transmission loss of sound into incubators: implications for voice perception by infants.

OBJECTIVE: To assess the transmission of sound into incubators as a function of talker position (i.e., standing or sitting), incubator port position (i.e., opened or closed), and center frequency (i.e., 125 to 10,000 Hz in one-third octave steps). The second objective was to estimate the audibility of the human voice inside the incubator. STUDY DESIGN: L(eq) measures of signal transmission loss and motor noise were obtained from two incubators. RESULTS: In general, signal transmission loss was greater for the standing-talker position, with front portholes closed, and for high-frequency spectra. Motor noise was greater with both front portholes closed and for lower-frequency spectra. The greatest signal delivery to an infant would be obtained when the speaker is sitting using a raised vocal effort while the incubator ports are opened. CONCLUSION: Measured signal transmission loss and motor noise characteristics of two incubators suggest that only mid-frequency speech spectra would be audible to infants and only at a speech-to-noise ratio of approximately 5 to 10 dB with a raised vocal effort.

Acoustics↗