Parents do not see GPs as source of help for emotionally disturbed schoolchildren.
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Affective Symptoms↗
Biomedical subjects
S Turner
Publications and source records attributed to S Turner.
Cloning and characterization of the promoter for the human complement factor I (C3b/C4b inactivator) gene.
Complement factor I is a serine proteinase that regulates the classical and alternative pathways of complement by cleaving C3b and C4b and preventing the assembly of C3 and C5 convertase enzymes. In order to understand the regulation of factor I gene expression in liver cells, 4kb of the 5' flanking region of the gene was cloned, and the 1474-bp 3'-end was sequenced and shown to contain a number of transcription factor consensus sequences. A major and two minor transcription start sites were identified, respectively, at 152, 178, and 198bp upstream of the translation start site by primer extension analysis. The transcriptional activity of the 1474-bp fragment was analyzed by fusion of 5' deletion constructs to a cat-encoding gene expression vector and transient transfections into Hep G2 cells. A 273-bp fragment located at -112 to +161 relative to the major transcription start site was sufficient for promoter activity. The 3' fragment spanning +3 to +161 and containing a TATA-like element did not demonstrate promoter activity, suggesting that the core promoter resides in a 115-bp sequence located between -112 and +3. This region contains an Inr-like element overlapping the major cap site and a CTF-NF1 element, two potential CCAAT boxes and an AP-2 element partially overlapping an Sp-1 site. Thus, factor I promoter may belong to the TATA-less Inr-driven class II promoters whose transcription is regulated by Sp-1. The transcriptional activity of the 1474-bp 5' flanking fragment was upregulated by PMA, IL-6 and TNF-alpha, suggesting that factor I may be an acute phase reactant.
Base Sequence↗
Unlicensed and off label drug use in paediatric wards: prospective study.
OBJECTIVE: To determine the extent of use in children in hospital of drugs that are not specifically licensed for use in children (unlicensed) and of drugs that are used outside the terms of their product licence that apply to indication, age, dose, or route of administration (off label). DESIGN: Prospective study of drugs administered on paediatric medical and surgical wards for 13 weeks. SETTING: Regional children's hospital. SUBJECTS: Paediatric inpatients in medical and surgical wards. MAIN OUTCOME MEASURES: Comparison of the use of each drug with its product licence to determine whether the drug was used in an unlicensed or off label manner. RESULTS: 2013 courses of drugs were administered to 609 paediatric patients in 707 admissions. 506 (25%) of the drug courses (prescriptions) were either unlicensed (139) or off label (367) uses. In 256 (36%) of the 707 admissions patients received one or more courses of an unlicensed or off label treatment in hospital. CONCLUSIONS: Use of drugs in an off label or unlicensed manner to treat children is widespread. Drugs are more likely to be used in an off label manner than in an unlicensed manner.
Adolescent↗
Influence of sterilization by gamma irradiation and of thermal annealing on creep of hydroxyapatite-reinforced polyethylene composites.
Sterilization of medical devices by gamma (gamma)-irradiation is common. The effect of irradiation on a bone replacement material, HAPEX (hydroxyapatite-reinforced polyethylene composite), was investigated. Unfilled and hydroxyapatite-filled polyethylene at 0.20 and 0.40 filler volume fractions were gamma-irradiated at 2.5 Mrad, and the modified properties were studied by differential scanning calorimetery, isochronous experiments, and creep tests. The effect of thermal annealing of the samples from 140 degrees C also was examined. The results suggest that both irradiation and annealing increase creep resistance of the materials. These are associated with the formation of crosslinks and an increase in crystallinity, respectively.
Biocompatible Materials↗
Hu23F2G, an antibody recognizing the leukocyte CD11/CD18 integrin, reduces injury in a rabbit model of transient focal cerebral ischemia.
Neutrophils are known to mediate injury in acute ischemic stroke especially during reperfusion. Migration of neutrophils into regions of ischemic injury involves binding to the endothelial cell's intercellular adhesion molecule (ICAM-1) through the leukocyte integrin, CD11/CD18. We studied the potential for neuroprotection with a humanized antibody that binds to and blocks the functions of the CD11/CD18 integrin in a rabbit model of transient focal ischemia. Fifteen New Zealand White rabbits underwent transorbital occlusion of the left middle cerebral, anterior cerebral, and internal carotid arteries using aneurysm clips for 2 h, followed by 6 h of reperfusion. Treatment with a maximally saturating dose (4 mg/kg) of a humanized CD11/CD18 monoclonal antibody (Hu23F2G, ICOS Corp., Bothell, WA) (n = 8) or placebo (n = 7) was administered 20 min after occlusion and given as a single intravenous bolus. Hemispheric ischemic neuronal damage (IND) as seen on hematoxylin- and eosin-stained sections was significantly reduced in Hu23F2G-treated animals by 57% (Hu23F2G: 15 +/- 6.9%; placebo: 35 +/- 5%; mean +/- SEM, P < 0.05, t-test). Immunohistochemical staining with neutrophil elastase confirmed the presence of neutrophils within regions of IND in control brains. Treatment with Hu23F2G resulted in marked reduction of neutrophil infiltration. (No. of neutrophils/IND area: Hu23F2G 36.1 +/- 36.7 cm-2, placebo 460.6 +/- 101.8 cm-2, P = 0.001. ) Antagonism of neutrophil migration at the level of the CD11/CD18 integrin reduces ischemic injury in experimental stroke.
Animals↗
Intersection accident estimation: the role of intersection location and non-collision flows.
This paper reviews models used in practice to relate accidents to traffic flows, with particular emphasis on the appropriateness of the model form and the statistical analysis technique employed for parameter estimation. The development of generalised linear models for predicting individual accident types at intersections in New Zealand is then described. The use of covariate analysis to identify the effect of intersection location, an investigation of the effect of non-collision flows, and the use of the models for predicting intersection accidents in three networks, are also described. It is concluded that generalised linear models for estimating different accident types (based on the conflicting flows) are better than models for estimating total accidents (based on the approach flows), especially when the cost of different accident types is known. It is also found that intersection location affects the number of different accident types, that it is important to consider the interactions between turning flows (to take better account of the mechanisms of accident occurrence), and that non-collision flows are sometimes important. Comparison of the predicted and observed numbers of accidents has shown that there is poor agreement for individual intersections, but fairly good agreement for networks.
Accidents, Traffic↗
Imaging the problem scaphoid.
Scaphoid fractures can be difficult to diagnose on X-ray, even at 2 weeks. We have compared prospectively bone scanning versus MRI scanning in 22 patients with persistent signs and symptoms suggestive of a scaphoid fracture at 2 weeks and found both methods to be sensitive, but MRI to be more specific, particularly in diagnosing soft tissue injuries like scapho-lunate ligament ruptures and triangular fibrocartilage tears. An early MRI scan at 2 weeks allows the clinician to make the appropriate decision in this group of patients whose diagnoses include; occult scaphoid fractures, other occult carpal and radial fractures, ligamentous injuries and those without apparent injuries. MRI has also been useful in defining the group of injuries which may imitate a clinically occult scaphoid fracture.
Adolescent↗
A comparative study of the 1992 and 1997 recovery positions for use in the UK.
In April 1997 the ILCOR Basic Life Support advisory statements were announced in conjunction with changes to the recovery position for use in the UK. This study compared the new and old positions by using a questionnaire to assess how well each position satisfied the ILCOR statements. The study was carried out over six different hospital trusts by eight resuscitation training officers. Each tutor alternately taught the 1992 or 1997 recommended positions. After the practical session each student completed a questionnaire on ease of learning and use of the position, as well as other factors such as spinal stability. They were also asked to score the position when they were placed in recovery by other students. Their competency was assessed using the ALS criteria. Over the duration of the study 687 forms were suitable for analysis. For every question there was a significant trend in favour of the 92 position, with students finding the technique easier to learn and use, simpler for positioning for CPR and with less spinal movement during rolling. Possible sources of bias such as previous training, tutor or staff grade made no statistical difference to the results. When performed competently the 1997 position appears to cause less brachial compression, but other problems with learning or use of the 97 position outweigh this advantage. The 1992 position currently provides the best compromise between ease of use, spinal stability and other factors, and better satisfies the ILCOR advisory statements.
Attitude of Health Personnel↗
Reliability and validity of the PAS-ADD Checklist for detecting psychiatric disorders in adults with intellectual disability.
The PAS-ADD Checklist is a screening instrument specifically designed to help staff recognize mental health problems in the people with intellectual disability for whom they care, and to make informed referral decisions. The instrument consists of a life-events checklist and 29 symptom items scored on a four-point scale. Scores are combined to provide three threshold scores. The crossing of any of these thresholds indicates the need for a fuller assessment. The items are worded in everyday language, making the Checklist suitable for use by individuals who do not have a background in psychopathology. The present paper presents the results of a number of studies evaluating the reliability and validity of the Checklist. Factor analysis of Checklists completed on a community sample of 201 individuals yielded eight factors, of which seven were readily interpretable in diagnostic terms. Internal consistency of the scales was generally acceptable. Inter-rater reliability in respect to individual items gave a fairly low average Kappa of 0.42. However, agreement on case identification, the main purpose of the Checklist, was quite good, with 83% of the decision being in agreement. Validity in relation to clinical opinion was also satisfactory, case detection rising appropriately with the clinically judged severity of disorder. The PAS-ADD Checklist is published and distributed by the Hester Adrian Research Centre, Manchester, England, from where further information and order forms are available on request.
Adolescent↗
Apoptosis, bcl-2 expression, and proliferative activity in human endometrial stroma and endometrial granulated lymphocytes.
Human endometrial leukocytes undergo regular cyclical changes during the menstrual cycle, with a striking increase in the phenotypically unusual population of CD56+ CD16- endometrial granulated lymphocytes (eGLs) in the late secretory phase and early pregnancy. The factors that regulate this increase in eGL numbers are unclear; their unusual morphology, however, has led to the suggestion that they undergo apoptosis at the end of the menstrual cycle. Apoptosis, bcl-2 expression, and proliferative activity were examined in the stroma of normal cycling, progesterone-treated, and early-pregnancy endometrium. The expression of bcl-2 and the Ki67 proliferation marker by highly purified (> 98% CD56+) eGLs from endometrium during the menstrual cycle and from first-trimester decidua was also studied. Apoptotic cells were rarely observed in the endometrial stroma of any of the samples examined. Stromal bcl-2 expression, however, increased from the proliferative to the premenstrual phase, and double immunohistochemical labeling demonstrated large numbers of bcl-2+ CD56+ eGLs. In contrast, Ki67 expression was high in the endometrial stroma during the proliferative phase, fell during the secretory phase, and rose again premenstrually, because of expression by eGLs. Isolated CD56+ eGLs also showed high bcl-2 and Ki67 expression at the end of the menstrual cycle. Unlike premenstrual endometrium, progesterone-treated endometrium and first-trimester decidua contained few proliferating cells, expressed high levels of bcl-2, and showed no evidence of apoptosis. Thus, eGLs do not undergo apoptosis in premenstrual endometrium, and their regulatory mechanisms remain to be clarified.
Apoptosis↗
Crystalline silica and risk of lung cancer in the potteries.
OBJECTIVE: To evaluate crystalline silica as a human carcinogen. METHODS: A cohort of 5115 men, born 1916-45 and employed in the pottery, refractory, and sandstone industries of Stoke-on-Trent was identified from occupations subject to health surveillance by the local Silicosis Medical Board (now the Department of Social Security). Detailed occupational and smoking histories, and records of small parenchymal opacities on periodic radiographs were extracted from medical records. An exposure matrix was derived from some 1400 personal or static dust samples and tested against the presence of small parenchymal opacities in a subcohort of 1080 men employed for at least 10 years, who had started working in the industry before 1960. RESULTS: Standardised mortality ratios (SMRs) calculated against mortalities for Stoke-on-Trent, with 95% confidence intervals (95% CIs), were raised for all causes (1.15 (1.05 to 1.26)), lung cancer (1.28 (0.99 to 1.62)) and non-malignant respiratory disease (2.04 (1.55 to 2.65)). Average concentration and duration of exposure to silica were, taken together, significantly related to the presence of small opacities (> or = 1/0). In a nested case-referent analysis of 52 cases of lung cancer and 197 matched referents, conditional logistic regression gave a significantly increased odds ratio (OR) for average silica concentration (micrograms/m3.100), after adjustment for smoking, of 1.66 (1.14 to 2.41) but not for duration of exposure nor, in consequence, for cumulative exposure. CONCLUSION: The association between risk of lung cancer and quantitative estimates of silica exposure supports the SMR analysis and implies that crystalline silica may well be a human carcinogen.
Aged↗
Metamotivational dominance and use of tobacco and alcohol among adolescents.
This study investigated differences in metamotivational dominance among adolescents who engaged in different amounts of substance use, specifically, whether students who labeled themselves as 'heavy' alcohol consumers or cigarette smokers would be more Paratelic and Negativism Dominant than those who labeled themselves 'nondrinkers' or 'nonsmokers'. 93 secondary school students (Years 9 and 10) participated in the study (68 boys, 25 girls). One-way analyses of variance indicated self-labeled heavy drinkers scored significantly more Paratelic Dominant than nondrinkers, while heavy smokers scored significantly more Paratelic and Negativism Dominant than nonsmokers. Paratelic Dominant adolescents who reported engaging in heavy smoking may have done so because smoking is defined by society as a risky behaviour and so provides arousal. Education and preventive programs that focus on health hazards of smoking may, in fact, increase the likelihood of this behaviour by both individuals who score Paratelic and Negativism Dominant.
Adolescent↗
Sustaining the unsustainable? City and society in Indonesia.
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Asia↗
Decreasing levels of fluoridation in the municipal water supply over the past six consecutive years.
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Environmental Monitoring↗
Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study.
Fluxes through intrahepatic glucose-producing metabolic pathways were measured in normal humans during overnight or prolonged (60 h) fasting. The glucuronate probe was used to measure the turnover and sources of hepatic UDP-glucose; mass isotopomer distribution analysis from [2-13C1]glycerol for gluconeogenesis and UDP-gluconeogenesis; [U-13C6]glucose for glucose production (GP) and the direct UDP-glucose pathway; and [1-2H1]galactose for UDP-glucose flux and retention in hepatic glycogen. After overnight fasting, GP (fluxes in milligram per kilogram per minute) was 2.19+/-0.09, of which 0.79 (36%) was from gluconeogenesis, 1.40 was from glycogenolysis, 0.30 was retained in glycogen via UDP-gluconeogenesis, and 0.17 entered hepatic UDP-glucose by the direct pathway. Thus, total flux through the gluconeogenic pathway (1.09) represented 54% of extrahepatic glucose disposal (2.02) and the net hepatic glycogen depletion rate was 0.93 (46%). Prolonging [2-13C1]glycerol infusion slowly increased measured fractional gluconeogenesis. In response to prolonged fasting, GP was lower (1. 43+/-0.06) and fractional and absolute gluconeogenesis were higher (78+/-2% and 1.11+/-0.07, respectively). The small but nonzero glycogen input to plasma glucose (0.32+/-0.03) was completely balanced by retained UDP-gluconeogenesis (0.31+/-0.02). Total gluconeogenic pathway flux therefore accounted for 99+/-2% of GP, but with a glycogen cycle interposed. Prolonging isotope infusion to 10 h increased measured fractional gluconeogenesis and UDP-gluconeogenesis to 84-96%, implying replacement of glycogen by gluconeogenic-labeled glucose. Moreover, after glucagon administration, GP (1.65), recovery of [1-2H1]galactose label in plasma glucose (25%) and fractional gluconeogenesis (91%) increased, such that 78% (0.45/0.59) of glycogen released was labeled (i.e., of recent gluconeogenic origin). In conclusion, hepatic gluconeogenic flux into glycogen and glycogen turnover persist during fasting in humans, reconciling inconsistencies in the literature and interposing another locus of control in the normal pathway of GP.
Carbon Isotopes↗
Additional approaches to DNA typing of skeletal remains: the search for "missing" persons killed during the last dictatorship in Argentina.
DNA typing techniques are among the most advanced tools for human identification and can contribute to the identification of poorly preserved skeletal remains. Ten thousand people are thought to have been killed during the last dictatorship in Argentina (1976-1983) and there are few official records on the identity of the victims or the location of burials. A mass grave containing 340 skeletons was excavated using archeological methods. A small number of individuals was identified by traditional forensic methods and one family group by mitochondrial DNA (mtDNA) analysis. Due to the lack of antemortem physical information on many of the victims, the application of molecular methods is imperative to speed up the identification process. We have tested two molecular screening methods, Y chromosome-specific short tandem repeats (DYS19, DYS385, DYS389 I, DYS389 II, DYS390, DYS391, DYS392, DYS393) and amplification of autosomal microsatellites using nested primers. These methods can complement solely matrilineal mtDNA sequence data in the identification of "missing" persons.
Argentina↗
Hepatic glucose-6-phosphatase flux and glucose phosphorylation, cycling, irreversible disposal, and net balance in vivo in rats. Measurement using the secreted glucuronate technique.
Measurement of hepatic glucose production (HGP) by standard isotope dilution reveals only the net release of glucose from the liver, not the flux across glucose-6-phosphatase ([G6Pase] or total hepatic glucose output), hepatic glucose cycling (HGC), irreversible glucose disposal into glycogen in the liver (hepatic Rd), or net hepatic glucose balance. We describe two independent isotopic techniques for measuring these parameters in vivo, both of which use secreted glucuronate (GlcUA). HGC can be quantified by measuring a correction factor for glucose label retained in hepatic glucose-6-phosphate (G6P), sampled as GlcUA. A complementary technique for measuring total hepatic glucose output is also described (reverse dilution), requiring administration of no labeled glucose but instead a labeled gluconeogenic precursor and unlabeled glucose. Hepatic Rd is calculated by multiplying the rate of appearance (Ra) of hepatic UDP-glucose ([UDP-glc] based on dilution of labeled galactose in GlcUA) times the direct entry of glucose into hepatic UDP-glc and the fraction of labeled UDP-glc retained in the liver. The sum of hepatic Rd plus HGC represents the total hepatic glucose phosphorylation rate. Rats received intravenous (i.v.) glucose infusions at a rate of 15 to 30 mg/kg/min after a 24-hour fast. Despite a suppression of net HGP more than 50%, total hepatic glucose output was not significantly decreased, because of increased HGC. Total hepatic glucose output calculated by reverse dilution yielded similar results during i.v. glucose infusions at 15 mg/kg/min, although values were higher than obtained by the correction-factor method at 30 mg/kg/min. The fraction of labeled UDP-glc released into blood glucose, representing a hepatic glycogen cycle, decreased from 35% (fasted) to nearly 0% (i.v. glucose 30 mg/kg/min). Hepatic Rd was 1.4, 4.6, and 7.5 mg/kg/min (fasted and i.v. glucose 15 and 30 mg/kg/min, respectively); total hepatic glucose phosphorylation increased substantially (from 4.2 to 8.5 to 12.7 mg/kg/min) and net hepatic glucose balance changed from negative to positive during i.v. glucose. In conclusion, hepatic G6Pase flux, glucose phosphorylation, HGC, disposal of glucose into glycogen, and net glucose balance can be measured noninvasively in vivo under various metabolic conditions by techniques involving the GlcUA probe.
Animals↗
Loss of heterozygosity in usual and special variant carcinomas of the endometrium.
Endometrial carcinoma is the most common invasive malignancy of the female genital tract, and it exists as two different clinicopathologic forms: an estrogen-dependent, "usual" type and an estrogen-independent "special variant" type. Despite the frequency of endometrial cancer, little is known about the molecular genetic events that contribute to its pathogenesis. The accumulation of genetic alterations identified through the study of loss of heterozygosity (LOH), gene mutation, and gene activation in tumor DNA has been associated with the establishment and progression of a variety of human malignancies. A relatively low incidence of LOH has been reported in usual type endometrial cancers; however, special variant tumors have rarely been included in the reported studies. To understand the molecular events that contribute to both forms of endometrial cancer, 31 tumors have been surveyed for events of LOH on all chromosomes. The study groups included 18 tumors of the usual type and 13 special variant tumors. Polymorphic loci were studied by Southern blot analysis and polymerase chain reaction (PCR) of microsatellite loci. Normal tissue in each case served as a control. Both frequency and patterns of LOH differed greatly between the two tumor types. Although LOH was frequently detected in the special variant tumors, it was rare in the usual type tumors. LOH was detected in only 8 of the 18 usual tumors, with chromosomes 17, 13, and 2 being the most frequently affected (22%, 20%, and 19%, respectively). In contrast, LOH was detected in all cases of special variant tumors, with chromosomes 17p, 14, and 12 showing the highest LOH (83%, 77%, and 40%, respectively). Two cases of microsatellite instability (MI) were detected among the usual type tumors. These findings suggest that the clinicopathologic phenotypes observed in these tumor types are likely caused by different tumorigenic pathways that reflect alterations of different cancer-controlling genes.
Blotting, Southern↗