A health impact assessment of increased aspirin use in Wales.
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Aspirin↗
Biomedical subjects
W R Williams
Publications and source records attributed to W R Williams.
Voltage-gated Na+ channel ligands and ATP: relative molecular similarity and implications for channel function.
The voltage-gated sodium channel (VGNC) is targeted by naturally occurring ligands and drugs of diverse structure. ATP modulates VGNC current in-vitro but is given little prominence in models describing channel function. This computational study uses superimposition and molecular fitting to investigate relative molecular similarity within the structures of ATP and VGNC ligands. A motif of 3 linked atoms (C-N-C) in the adenine ring of ATP satisfies the fitting of a wide range of anticonvulsant structures. An alternative group (N-C-N) provides one fitting motif for the ester and amide groups of local anaesthetic drugs; protonated amine and aromatic groups in the same conformers fit to a second motif in the adenine ring. Analogous structures from other drug classes with VGNC blocking activity give the same molecular fits to ATP. Structures fitted to the adenine ring of ATP occlude the intra-molecular space between the nucleoside and triphosphate chain in approximation to their established blocking, activating or neutral effects on Na+ current. The findings are discussed in terms of drug preferences for VGNC states and channel requirements for ATP.
Adenosine Triphosphate↗
Reduced tuberculin reactions with a single-use Heaf gun.
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Adolescent↗
Hyperopia and educational attainment in a primary school cohort.
BACKGROUND: Vision screening addresses the visual impairments that impact on child development. Tests of long-sightedness are not found in most school screening programmes. The evidence linking mild-moderate hyperopia and lack of progress in school is insufficient, although strengthened by recent findings of developmental problems in infants. AIMS: To report on the relation between hyperopia and education test results in a cohort of primary school children. METHODS: A total of 1298 children, aged 8 years, were screened for hyperopia on the basis of fogging test results. School test results (NFER and SATs) were compared between groups categorised by referral status and refractive error. RESULTS: A total of 166 (12.8%) fogging test failures were referred for ophthalmic assessment. Ophthalmic tests on 105 children provided an accurate diagnosis of vision defects, for reference to their education scores. Fifty per cent of the children examined by optometrists required an intervention (prescription change, glasses prescribed, or referral). Mean (95% CI) NFER scores of children with refractive errors (summed for both eyes) >+3D (98.4, 93.0-103.8, n = 32) or >+1.25D (best eye) (99.3, 93.0-105.6, n = 26) were lower than the respective scores of children with a less positive refractive state (104.8, 100.7-108.9, n = 43) (103.6, 99.7-107.4, n = 49), the non-referred group, and total sample. The SATs results followed a similar trend. A high proportion of the fogging test failures (16%) and confirmed hyperopes (29%) had been referred to an educational psychologist, and the latter group contributed substantially to the poor education scores. CONCLUSIONS: The results of this study provide further evidence for a link between hyperopia and impaired literacy standards in children.
Analysis of Variance↗
Receptor regulatory properties evident in the molecular similarity of serotonin receptor ligands and purine nucleotides.
Previous computational studies have explored the relative molecular similarity inherent in the ligands of neurotransmitter-regulated cell receptors and purine nucleotides. This study presents the results of an investigation of the major serotonin (5-HT) receptor classes, using molecular superimposition and fitting data. Ligands for 5HT(1B/C/D) and 5HT(4/7) receptors identified pharmacophores in the adenine ring of ATP. 5-HT(2) and 5-HT(3) receptor ligands identified pharmacophores in the guanosine nucleotide and cyclic nucleotide, respectively. The described molecular similarity is consistent with the cyclic nucleotide responses observed during signal transduction events initiated by 5-HT, and the reported similarity between ligands of the 5-HT(1B) and 5-HT(1D), 5-HT(1A) and 5-HT(7), and 5-HT(4) and 5-HT(3) receptors. The results are discussed in terms of current pharmacophoric models and signal transduction events involving interaction between G-protein receptors and catalytic sites.
Binding Sites↗
Accidents in the school environment: perspectives of staff concerned with data collection and reporting procedures.
School-accident reports document incidents that have resulted in children requiring assistance from staff in the education and healthcare sectors. This study was undertaken to investigate the collection and use of data by agencies concerned with the school-accident problem. Our aim was to determine if the annual collection and use of such a large body of data might be improved through better management procedures. Interviews were conducted with primary and secondary school staff in one education authority. Interviewees completed a questionnaire on accident activity and accident reporting in their school. In the healthcare sector, staff from the Schools' Office and the ambulance unit servicing the schools provided information on their collection and use of data. Our survey found that accident activity is usually a private matter for individual schools, shared to varying degrees with the education authority. Playgrounds, children's behaviour and footwear carried much of the blame for the injuries sustained. Staff generally accepted the current accident rates. The compilation of accident data by the Schools' Office, accident and emergency department, and ambulance service were compromised by deficiencies in computerization and computer software. The management and utilization of school-accident data could be improved by better collaboration within and between the education and healthcare agencies.
Accident Prevention↗
Secondary school accident reporting in one education authority.
BACKGROUND: Secondary schools appear to have very different accident rates when they are compared on the basis of accident report returns. The variation may be as a result of real differences in accident rates or different reporting procedures. This study investigates accident reporting from secondary schools and, in particular, the role of the school nurse. METHODS: Accident form returns covering a 2-year period were collected for statistical analysis from 13 comprehensive schools in one local education authority in Wales. School sites were visited in the following school year to obtain information about accident records held on site and accident reporting procedures. RESULTS: The main factors determining the number of school accident reports submitted to the education authority relate to differences in recording and reporting procedures, such as the employment of a nurse and the policy of the head teacher/safety officer on submitting accident returns. Accident and emergency department referrals from similar schools may show significant differences in specific injuries and their causes. CONCLUSIONS: The level of school accident activity cannot be gauged from reports submitted to the education authority. Lack of incentives for collecting good accident data, in conjunction with the degree of complacency in the current system, suggest that future accident rates and reporting activity are unlikely to change.
Accidents↗
Primary school accident reporting in one education authority.
BACKGROUND: Studies have shown a correlation between increased accident rates and levels of deprivation in the community. School accident reporting is one area where an association might be expected. AIMS: To investigate differences in primary school accident rates in deprived and more affluent wards, in an area managed by one education authority. METHODS: Statistical analysis of accident form returns for 100 primary schools in one education authority in Wales over a two year period, in conjunction with visits to over one third of school sites. RESULTS: Accident report rates from schools in deprived wards were three times higher than those from schools in more affluent wards. School visits showed that this discrepancy was attributable primarily to differences in reporting procedures. One third of schools did not report accidents and approximately half did not keep records of minor accidents. CONCLUSIONS: The association between school accident report rates and deprivation in the community is complex. School accident data from local education authorities may be unreliable for most purposes of collection.
Accidents↗
Receptor regulatory properties evident in the molecular similarity of dopamine receptor ligands and purine nucleotides.
Computational studies have revealed similarities in the relative configurations of purine nucleotides and ligands for histamine, acetylcholine and adrenergic receptors. In common with other G-protein-regulated receptors, dopamine receptors are associated with specific changes in nucleotide levels during signal transduction processes. The purpose of this study was to investigate molecular similarity in dopamine receptor ligands and purine nucleotides. Molecular superimposition and fitting data for D1-like receptor ligands identified a pharmacophore in the adenine and ribose rings of ATP. D2-like agonists and antagonists related to a pharmacophore in the guanine and ribose rings of GTP. The results are consistent with the hypothesis that the dopamine receptor family may have evolved from receptors for the ATP and GTP nucleotides.
Adenosine Triphosphate↗
Near-precise interchromosomal recombination and functional DNA topoisomerase II cleavage sites at MLL and AF-4 genomic breakpoints in treatment-related acute lymphoblastic leukemia with t(4;11) translocation.
We analyzed the der(11) and der(4) genomic breakpoint junctions of a t(4;11) in the leukemia of a patient previously administered etoposide and dactinomycin by molecular and biochemical approaches to gain insights about the translocation mechanism and the relevant drug exposure. The genomic breakpoint junctions were amplified by PCR. Cleavage of DNA substrates containing the normal homologues of the MLL and AF-4 translocation breakpoints was examined in vitro upon incubation with human DNA topoisomerase IIalpha and etoposide, etoposide catechol, etoposide quinone, or dactinomycin. The der(11) and der(4) genomic breakpoint junctions both involved MLL intron 6 and AF-4 intron 3. Recombination was precise at the sequence level except for the overall gain of a single templated nucleotide. The translocation breakpoints in MLL and AF-4 were DNA topoisomerase II cleavage sites. Etoposide and its metabolites, but not dactinomycin, enhanced cleavage at these sites. Assuming that DNA topoisomerase II was the mediator of the breakage, processing of the staggered nicks induced by DNA topoisomerase II, including exonucleolytic deletion and template-directed polymerization, would have been required before ligation of the ends to generate the observed genomic breakpoint junctions. These data are inconsistent with a translocation mechanism involving interchromosomal recombination by simple exchange of DNA topoisomerase II subunits and DNA-strand transfer; however, consistent with reciprocal DNA topoisomerase II cleavage events in MLL and AF-4 in which both breaks became stable, the DNA ends were processed and underwent ligation. Etoposide and/or its metabolites, but not dactinomycin, likely were the relevant exposures in this patient.
Antigens, Neoplasm↗
Structure of outcome beliefs in condom use. The Project RESPECT Study Group.
To study the structure of beliefs about condom use outcomes, the authors derived and tested 4 psychosocial hypothetical models: (a) a 2-factor model of the personal and social outcomes of condom use; (b) a 2-factor model of the pros and cons of the behavior; (c) a 3-factor model (i.e., physical, self-evaluative, and social) of outcome expectancies; and (d) a thematic 4-factor model of the protection, self-concept, pleasure, and interaction implications of the behavior. All 4 models were studied with a confirmatory factor analysis approach in a multisite study of 4,638 participants, and the thematic solution was consistently the most plausible. Self-concept and pleasure were most strongly associated with attitudes toward using condoms, intentions to use condoms, and actual condom use, whereas protection and interaction generally had little influence.
Adult↗
Discontinuation, leaving reasons and course evaluation comments of students on the common foundation programme.
There is considerable financial incentive, at all levels, to reduce student nurse wastage and maintain recruitment to a workforce of professional nurses. This strategy is being pursued in a period following major educational change, when the attrition levels and leaving reasons of students need to be reassessed. Previous reports have identified a high voluntary loss of students on the common foundation programme (CFP) of the pre-registration nursing course. In order to achieve a better understanding of the basic problems faced by student nurses who consider leaving the CFP, questionnaires were distributed to three groups of students: current CFP students; students who had completed the CFP; and students who had discontinued training. The questionnaire responses show that course-based problems, identified as prime leaving reasons by the current and completed student groups, differ from the actual leaving reasons of discontinued students obtained by exit questionnaire. The attitudes of participating and discontinued students to theory, clinical and pastoral components of the CFP are not dissimilar. Some trends in attrition rate relate significantly to student category. Our results have implications for the management of student nurse attrition.
Adult↗
Student nurse satisfaction: implications for the common foundation programme.
This decade has seen a major restructuring of pre-registration nurse education within the higher education system that was costly and initially largely unpopular with qualified nurses and students. Major flaws have been identified in the common foundation programme (CFP) and student attrition rates remain too high. Our detailed survey of student satisfaction within the CFP shows that clinical placement is the most popular course component and that poor organization remains the worst aspect of the course. Teaching was more highly regarded than the organizational component of the course, although students found room for improvement. Core teaching modules such as bioscience and nursing interventions achieved better ratings than supporting modules, for example social policy or research and reflection on practice. The establishment of contact between personal tutors and students appeared to be slow. The described deficiencies have since been addressed in curriculum planning and the development of new course structure.
Adult↗
Chronic and recovered cases of sheep-associated malignant catarrhal fever in cattle.
Malignant catarrhal fever (MCF) is traditionally regarded as a disease with a short clinical course, low morbidity and high case fatality rate. Owing to the limitations of the assays used for laboratory diagnosis. It was difficult in characterise the clinical spectrum of sheep-associated MCF, particularly when the cattle recovered from an MCF-like clinical syndrome. Over a period of three years, 11 cattle that survived MCF for up to two-and-a-half years were identified on four premises. A clinical diagnosis of MCF was confirmed by the detection of ovine herpesvirus-2 DNA in peripheral blood leucocytes using a polymerase chain reaction (PCR) assay that detects a specific 238 base-pair fragment of viral genomic DNA. Of the 11 cattle examined, six recovered clinically with the exception of bilateral corneal oedema with stromal keratitis (four animals) and unilateral perforating keratitis (one animal). The 10 animals available for postmortem examination had disseminated subacute to chronic arteriopathy. Recovery was associated with the resolution of the acute lymphoid panarteritis that characterises the acute phase of MCF, and with the development of generalised chronic obliterative arteriosclerosis. Bilateral leucomata were due in part to the focal destruction of corneal endothelium secondary to acute endothelialitis. Formalin-fixed tissues and/or unfixed lymphoid cells from all 11 cattle were positive for sheep-associated MCF by PCR. These observations indicate that recovery and chronic disease are a significant part of the clinical spectrum of MCF and that such cases occur with some frequency in the area studied. The affected cattle remain persistently infected by the putative sheep-associated MCF gammaherpesvirus.
Animals↗
Hypersensitivity to dexamethasone.
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Dexamethasone↗
The Li-Fraumeni syndrome: from clinical epidemiology to molecular genetics.
The goal of this review is to demonstrate the effective interaction of epidemiologic methods and molecular genetics in the identification of familial cancer predisposition. The example involves a hospital-based population of childhood soft tissue sarcoma patients who were less than age 16 years at diagnosis at the University of Texas M. D. Anderson Cancer Center, Houston, Texas, in 1944 through 1976, had survived at least 3 years from diagnosis, and were diagnosed at least 5 years before the start of our study. Familial data were collected on the patients' offspring, full siblings, parents, aunts, uncles, and grandparents. The initial analysis revealed a small but significant cancer excess in first-degree relatives. Genetic analysis demonstrated that the cancer distribution in families could best be explained by a rare autosomal dominant gene with penetrance such that the risk of cancer by age 35 years was nearly 50%. Most of the evidence for a dominant gene came from nine kindreds. Laboratory investigation of fibroblasts from those kindreds provided an in vitro model of cellular immortalization and carcinogenesis. Germline mutations in the tumor suppressor gene p53 were found in two of the families, and studies are ongoing in the other kindreds. This review demonstrates the power of genetic epidemiologic methods to characterize statistically a cancer-predisposing gene and the application of molecular genetics to define the genetic defect.
Adolescent↗
In vitro displacement of vasoactive mediators from plasma proteins: a possible mechanism for pseudo-allergic reactions to neuromuscular blocking drugs.
We have studied the release of prostaglandin F2 alpha (PGF2 alpha) and histamine from serum proteins by neuromuscular blocking drugs using equilibrium dialysis, with tracer quantities of radio-labelled mediators as probes. Small concentrations (0.05-0.25 mmol litre-1) of competitive neuromuscular blocking drugs displaced 16-67% of bound histamine. Greater concentrations of suxamethonium (2 mmol litre-1) were required for histamine displacement (19%). There was a significant release of PGF2 alpha by atracurium 1 mmol litre-1 and pancuronium 0.69 mmol litre-1. These findings suggest an alternative mechanism of histamine release by neuromuscular blocking drugs which may be relevant to adverse reactions during use.
Blood Proteins↗
Sensitivity of Salmonella typhimurium TA97a to the type of agar used for preparation of Vogel-Bonner plates.
Recent problems with the supply of Difco bacto agar have forced some laboratories to evaluate alternative agars for use in the Salmonella/microsome assay. This led to the independent observation in two laboratories (Boots and Glaxo) that Salmonella typhimurium TA97a is sensitive to certain types of agar that may be used to prepare Vogel-Bonner minimal medium plates. A programme of work was, therefore, undertaken to investigate this phenomenon; 9-aminoacridine hydrochloride (at Boots) and 4-nitro-o-phenylenediamine (at Glaxo) were tested against TA1537 and TA97a using Vogel-Bonner plates prepared with a number of different agars. Three agars (Lab M, Difco Bi-tek and Beckton Dickinson granulated) were identified which, although supporting normal growth of TA1537 revertant colonies, gave much reduced control counts and responses to the mutagens with TA97a. One agar, Becton Dickinson grade A, gave poor responses with TA1537 but produced satisfactory results with TA97a. In contrast to the Vogel-Bonner plates, varying the type of agar used in the top agar overlays had little effect on the responses obtained. On the basis of these comparisons, Becton Dickinson purified agar was selected as a suitable alternative to Difco bacto and it was concluded that laboratories using agars other than these, or purchasing pre-poured plates without specifying the type of agar, should be made aware of potential problems with TA97a.
Agar↗