On the evidence. Schizophrenia.
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Cognitive Behavioral Therapy↗
Biomedical subjects
P Wilson
Publications and source records attributed to P Wilson.
Changes in the natural history of cytomegalovirus retinitis following the introduction of highly active antiretroviral therapy.
OBJECTIVE: To determine the effect of highly active antiretroviral therapy (HAART) on the natural history of cytomegalovirus (CMV) retinitis. DESIGN AND PARTICIPANTS: Retrospective analysis of 103 consecutive patients diagnosed with CMV retinitis between 1990 and 1998. SETTING: Specialist HIV medicine department of a London hospital. MAIN OUTCOME MEASURES: Incidence of CMV retinitis, time to death following diagnosis, episodes of progression, incidence of inflammatory complications. The date of first use of HAART was January 1995. Data were censored on 30 June 1998. RESULTS: The incidence of CMV retinitis has declined dramatically following the introduction of HAART. Survival following CMV retinitis increased from a median of 0.65 years prior to 1995 to a median of 1.07 years after this date (P = 0.004). In multivariate analyses HAART was independently associated with improved survival (P = 0.02) and the association with year of diagnosis was no longer significant, suggesting that this effect is predominantly due to HAART. None of the patients receiving HAART experienced progression after 6 months of treatment. Complications of retinitis such as retinal detachment, uveitis and optic atrophy occurred in 39% of patients. The rare inflammatory complications of vitritis and cystoid macular oedema occurred only in recipients of HAART. CONCLUSIONS: The introduction of HAART has had a major impact on the natural history of CMV retinitis with improved survival time and decreased risk of progression following diagnosis. However, immune reconstitution may be associated with inflammatory complications which can result in significant visual loss in the absence of active CMV disease.
AIDS-Related Opportunistic Infections↗
Transverse momentum and total cross section of e(+)e(-) pairs in the Z-boson region from p&pmacr; collisions at sqrt
The transverse momentum and total cross section of e(+)e(-) pairs in the Z-boson region of 66<M(ee)<116 GeV/c(2) from p&pmacr; collisions at sqrt[s] = 1.8 TeV are measured using 110 pb(-1) of collisions taken by the Collider Detector at Fermilab during 1992-1995. The total cross section is measured to be 248+/-11 pb. The differential transverse momentum cross section is compared with calculations that match quantum chromodynamics perturbation theory at high transverse momentum with the gluon resummation formalism at low transverse momentum.
Journal Article↗
Measurement of the helicity of W bosons in top quark decays
We use the transverse momentum spectrum of leptons in the decay chain t-->bW with W-->lnu to measure the helicity of the W bosons in the top quark rest frame. Our measurement uses a t&tmacr; sample isolated in 106+/-4 pb(-1) of data collected in p&pmacr; collisions at sqrt[s] = 1.8 TeV with the CDF detector at the Fermilab Tevatron. Assuming a standard V-A weak decay, we find that the fraction of W's with zero helicity in the top rest frame is F0 = 0.91+/-0. 37(stat)+/-0.13(syst), consistent with the standard model prediction of F0 = 0.70 for a top mass of 175 GeV/c(2).
Journal Article↗
Observation of diffractive b-quark production at the fermilab tevatron
We report a measurement of the fraction of b quarks produced diffractively in &pmacr;p collisions at sqrt[s] = 1.8 TeV. Diffraction is identified by the absence of particles in a forward pseudorapidity region. From events with an electron of transverse momentum 9.5<p(e)(T)<20 GeV/ c within the pseudorapidity region |eta|<1.1, the ratio of diffractive to total b-quark production rates is found to be R(&bmacr;b) = [0.62+/-0.19(stat)+/-0.16(syst)]%. This result is comparable in magnitude to corresponding ratios for W and dijet production but significantly lower than expectations based on factorization.
Journal Article↗
Identification of peanut and hazelnut allergens by native two-dimensional gel electrophoresis.
A procedure for the native two-dimensional electrophoresis of peanut and hazelnut proteins is described. Proteins were solubilised after acetone treatment using a combination of 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) and tetramethylene sulphone. These extracts were analysed by a combination of isoelectric focusing in the presence of lactose in immobilized pH gradients followed by charge shift electrophoresis. Immunoblot analysis, using sera from nut allergic patients, allowed the identification of a peanut and hazelnut allergen with identical isoelectric point and apparent molecular mass. These proteins were recovered from duplicate gels using a mixture of formic acid, acetonitrile (ACN) and isopropanol. The molecular masses for both proteins, determined by matrix assisted laser desorption/ionisation-mass spectrometry (MALDI-MS), were 4826 Da.
2-Propanol↗
The effect of an external load on the force and timing components of mentally represented actions.
The chronometry of real and imagined movements was investigated in a group of eight subjects under varying conditions. The visually-guided pointing task was used to investigate the speed for accuracy trade-offs that occur as target size is varied for both real and imagined performance. The task was performed both with and without an external load of 2 kg. For the no-load condition and load conditions, the speed for accuracy trade-off for both real and imagined performance conformed to Fitts' law. Movement durations of real movements remained largely unaffected by the addition of the load, however, movement durations of imagined movements increased significantly with the addition of the load. These patterns of results suggest that the weight disrupted the force calculation component of imagined movements but not the relative timing.
Adult↗
A dose-finding study of raltitrexed (tomudex) with cisplatin and epirubicin in advanced gastro-oesophageal adenocarcinoma.
The standard treatment for advanced gastro-oesophageal cancer in the UK is epirubicin, cisplatin and continuous infusion 5-fluoruracil by an indwelling central venous catheter (ECF), which has significant morbidity. Raltitrexed (tomudex), a specific inhibitor of thymidylate synthase with a long plasma terminal half-life (50-100 h) has activity in gastro-intestinal tract malignancy. To reduce the Hickman line-associated morbidity of ECF; we have conducted a dose-finding study of tomudex combined with epirubicin and cisplatin. Twenty-four patients (22 males, two female), median age 63 years (range 21-75), ECOG performance status < or =2 with histologically proven, unresectable or metastatic gastric (14 patients), gastro-oesophageal junction (nine patients) or oesophageal (one patient) adenocarcinoma received treatment with 3-weekly cisplatin 60 mg m(-2), epirubicin 50 mg m(-2) and tomudex at doses of 2 mg m(-2), 2.5 mg m(-2) or 3 mg m(-2) in successive cohorts. Six patients were treated per dose level with no intra-patient dose escalation. Dose escalation occurred after six patients had completed at least one cycle of chemotherapy at the previous dose level. After defining the maximum tolerated dose a further six patients were treated at the preceding dose level to assess toxicity at the proposed phase II dose. A total of 102 cycles (50% completed 6 cycles) were administered. The dose-limiting toxicities are neutropenia and diarrhoea occurring in 2/6 patients at the 3 mg m(-2) dose level. Of those patients evaluable for response, there were eight partial and one complete response (overall response rate 38%). The median survival was 9.9 months. ECT is an active regimen in oesophagogastric adenocarcinoma. The recommended dose of tomudex for further study in combination with epirubicin and cisplatin is 2.5 mg m(-2).
Adenocarcinoma↗
Drug treatments for schizophrenia.
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Antipsychotic Agents↗
Psychosocial interventions for schizophrenia.
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Humans↗
Exogenous surfactant supplementation in infants with respiratory syncytial virus bronchiolitis.
Infants with respiratory syncytial virus (RSV) bronchiolitis are deficient in surfactant, both in quantity and ability to reduce surface tension. New evidence suggests surfactant has a role in maintaining the patency of conducting airways, which has implications for RSV bronchiolitis. A randomized, controlled pilot study was undertaken to assess the effects of exogenous surfactant supplementation to RSV-positive infants on pulmonary mechanics, indices of gas exchange, and the phospholipid composition of bronchoalveolar lavage fluid (BALF). Nineteen ventilated infants (median corrected age 4 wk) received either two doses of surfactant (Survanta, 100 mg/kg) within 24 and 48 h of mechanical ventilation (n = 9), or air placebo (n = 10). Static lung compliance and resistance of infants in the placebo but not in the surfactant-treated group became progressively worse over the first 30 h following enrollment. Although no significant acute changes in gas exchange parameters were seen following surfactant, infants in the surfactant group showed a more rapid improvement in oxygenation and ventilation indices over the first 60 h of ventilation. Surfactant status was assessed from the concentration ratio in BALF of the disaturated phospholipid species dipalmitoylphosphatidylcholine to that of the monounsaturated species palmitoyloleoylphosphatidylcholine. This ratio correlated with both lung compliance (positively) and resistance (negatively), and over time increased in the treated group and declined in placebo infants. The data from this pilot study suggest that functional surfactant has a role in maintaining small airway patency as well as lung compliance in infants infected with RSV and an outcome study is now warranted.
Bronchiolitis, Viral↗
The effectiveness and cost-effectiveness of prophylactic removal of wisdom teeth.
BACKGROUND: Removal of wisdom teeth is one of the most common surgical procedures performed in the UK. Little controversy surrounds the removal of impacted third molars when they are associated with pathological changes such as infection, non-restorable carious lesions, cysts, tumours, and destruction of adjacent teeth and bone. However, the justification for prophylactic removal of impacted third molars is less certain and has been debated for many years. OBJECTIVES: To provide a summary of existing evidence on prophylactic removal of impacted wisdom teeth, in terms of the incidence of surgical complications associated with prophylactic removal, and the morbidity associated with retention. METHODS: A systematic review of the research literature was undertaken. METHODS - DATA SOURCES: An existing review formed the basis of this report, and additional literature searches were undertaken, including searches of electronic databases (MEDLINE, 1984-99; EMBASE, 1984-99; Science Citation Index, Cochrane Controlled Trials Register, National Research Register; Database of Abstracts of Reviews of Effectiveness), paper sources (including Clinical Evidence), and web-based resources. Relevant organisations and professional bodies were contacted for further information. METHODS - STUDY SELECTION: Studies were selected for inclusion if they met the following criteria: (1) design - randomised controlled trials (RCTs), literature reviews, or decision analyses; (2) participants - people with unerupted or impacted third molars, or those undergoing surgical removal of third molars either as prophylaxis or due to associated pathological changes; (3) reported outcomes - either the pathological changes associated with retention of third molars, or post-operative complications following extraction. There were no language restrictions on study selection. METHODS - DATA EXTRACTION AND SYNTHESIS: Data from included studies were extracted into structured tables and individual study validity was assessed against methodological checklists. Data were summarised descriptively. Decisions relating to study selection, data extraction and validity assessment were made by two independent reviewers, and disagreements were resolved by discussion. For non-English papers, translators were recruited to assist with study selection and data extraction. RESULTS: Forty studies were included in the review: two RCTs, 34 literature reviews, and four decision analysis studies. One RCT in the UK focused on the effects of retained third molars on incisor crowding (predominantly a cosmetic problem) in patients who had previously undergone orthodontic treatment. The results of this trial suggested that the removal of third molars to prevent late incisor crowding cannot be justified. Another on-going RCT in Denmark compares the effects and costs of prophylactic removal of third molars with removal according to morbidity. So far, this trial has recruited 200 participants, and preliminary results indicate that watchful waiting may be a promising strategy. However, more data and longer follow-up of patients are needed to conclude which treatment strategy is the most cost-effective. It is also known that a trial is on-going in the USA but no results are available so far. The methodological quality of the literature reviews was generally poor, and none of the reviews was systematic. Conclusions from nine reviews on anterior crowding suggested that there was only a weak association between retention of third molars and crowding. Six out of 21 reviews with a more general scope also concluded that the prophylactic removal of third molars was unjustified. Twelve general reviews did not conclude with a clear message about the management of third molars. Three reviews suggested that prophylactic removal of third molars is appropriate, but these reviews were of poorer methodological quality than the majority of other reviews. Three out of four papers focusing on surgical management expressed
Cost-Benefit Analysis↗
Social variation in reasons for contacting general practice out-of-hours: implications for daytime service provision?
BACKGROUND: Contact with general practice out-of-hours services increases with socioeconomic deprivation. The reasons for this association are unclear but may include variations in access to daytime services or differences in morbidity. AIM: To identify the reasons for contact with the Glasgow Emergency Medical Service (GEMS) in relation to patient sociodemographic characteristics and the nature of the presenting problem. METHOD: All contacts with GEMS over a one-week period (n = 3193) in October 1996 were identified and a random 1:2 sample were sent a postal questionnaire investigating their reasons for contacting the service. Sociodemographic data and presenting problems were extracted from the service contact sheet. Data were analysed using correspondence analysis. RESULTS: Correspondence analysis identified two factors characterised as 'perceived problems with daytime services' and 'perceived urgency'. Scores on the former dimension were significantly associated with age (P < 0.0001), gender (P < 0.0001), socioeconomic category (P < 0.0001), and presenting problem (P = 0.015) and scores were higher in adults, in males, among the non-affluent (particularly those resident in deprived areas), and in those presenting with a musculoskeletal problem. Scores on the latter dimension were significantly associated with age (P < 0.0001) and presenting problem (P < 0.0001). Scores tended to increase after childhood and for each of the five most frequent categories of presenting problem relative to other symptoms. CONCLUSIONS: Compared to those from affluent areas, patients from non-affluent areas appear to perceive difficulties accessing their general practitioner during surgery hours and may contact out-of-hours services as an alternative.
Adolescent↗
Histochemical mapping of the substrate for brain-stimulation reward with glycogen phosphorylase.
Glycogen phosphorylase is the enzyme that regulates glycogenolysis and it appears that there is a relationship between central levels of glycogen and neuronal activity, which is influenced by a variety of neurotransmitters. In the present study, glycogen phosphorylase histochemistry was used to correlate changes in metabolic activity in response to rewarding lateral hypothalamic stimulation. Rats were allowed to self-stimulate for 1 h per day for ten consecutive days following which postmortem phosphorylase a activity was examined. Significant differences in optical density between the stimulated and contralateral hemispheres were found in three of the eight analyzed structures, two of which, the diagonal band of Broca and the caudate nucleus, showed a greater density of glycogen phosphorylase a on the stimulated side and the third, the habenula, had greater contralateral activity. In conclusion, our data suggest that glycogen phosphorylase activity is a viable but not weighty marker of energy alterations induced by chronic exposure to intracranial self-stimulation, and that it is generally consistent with the patterns revealed by other metabolic indices such as cytochrome oxidase and 2-deoxyglucose autoradiography.
Animals↗
Muscle as the primary site of urea cycle enzyme activity in an alkaline lake-adapted tilapia, Oreochromis alcalicus grahami.
The tilapia fish Oreochromis alcalicus grahami from Kenya has adapted to living in waters at pH 10.5 by excreting the end product of nitrogen metabolism as urea rather than as ammonia directly across the gills as occurs in most fish. The level of activity in liver of the first enzyme in the urea cycle pathway, carbamoyl-phosphate synthetase III (CPSase III), is too low to account for the observed high rates of urea excretion. We report here the surprising finding that CPSase III and all other urea cycle enzyme activities are present in muscle of this species at levels more than sufficient to account for the rate of urea excretion; in addition, the basic kinetic properties of the CPSase III appear to be different from those of other known type III CPSases. The sequence of the CPSase III cDNA is reported as well as the finding that glutamine synthetase activity is present in liver but not in muscle. This unusual form of adaptation may have occurred because of the apparent impossibility of packaging the needed amount of urea cycle enzymes in liver.
Adaptation, Physiological↗
beta-catenin mutation and expression analysis in ovarian cancer: exon 3 mutations and nuclear translocation in 16% of endometrioid tumours.
The molecular mechanisms involved in the generation of epithelial ovarian cancers are poorly understood, but evidence suggests that the different histological subtypes may arise from independent tumorigenic events. beta-Catenin is emerging as an important oncogene in the transformation of a number of epithelial cancers, and mutations have been reported in a small study of endometrioid ovarian adenocarcinomas. Mutations in the NH(2)-regulatory domain of beta-catenin stabilise the cytoplasmic levels of this protein, which promotes up-regulation of the beta-catenin-T-cell factor-lymphoid enhancer factor transcriptional complex. We report here beta-catenin (CTNNB1) exon 3 mutation analysis in 149 epithelial ovarian carcinomas. This revealed 10/63 (16%) endometrioid ovarian tumours with activating mutations of the beta-catenin gene. All mutations were missense changes within the GSK3beta consensus site, affecting serine residues at codons 33 and 37 and glycine at codon 34. Immuno-histochemical analysis identified cytoplasmic stabilisation and nuclear translocation in those endometrioid tumours with mutations. This phenotypic change was also identified in 3 other endometrioid tumours that did not have somatic mutations within exon 3 of CTNNB1. Stabilisation of the free, monomeric pool of beta-catenin and the probable resulting constitutive activation of its Tcf-associated transcriptional complex appears to be a specific oncogenic event in endometrioid ovarian adenocarcinoma.
Biological Transport↗
Loss of cytomegalovirus (CMV) viraemia following highly active antiretroviral therapy in the absence of specific anti-CMV therapy.
OBJECTIVE: To determine the effect of highly active antiretroviral therapy (HAART) on cytomegalovirus (CMV) viraemia and retinitis in patients at high risk of disease. DESIGN: Sixteen patients with CMV viraemia, but no evidence of end organ disease at the time of first receipt of HAART including a protease inhibitor, were studied. No patient had ever received specific anti-CMV therapy. METHODS: CMV load in blood was measured using quantitative competitive PCR at baseline and for a median follow-up of 21 months. Regular ophthalmological screening for retinitis was conducted throughout the study period. RESULTS: All 16 patients became CMV negative by PCR following the commencement of HAART. CMV loads prior to treatment ranged from 2.0 x 10(3) to 4.1 x 10(6) copies/ml (median, 7.6 x 10(4) copies/ml). The median time to becoming PCR negative was 13.5 weeks (range, 5-40 weeks). Fourteen patients remained CMV negative throughout follow-up. CMV viraemia recurred in two patients; these individuals were indistinguishable with respect to either baseline parameters or response to antiretroviral therapy. None of the 16 patients developed CMV retinitis. CONCLUSIONS: HAART including a protease inhibitor can result in the complete suppression of CMV viraemia, an effect not previously observed in HIV-infected patients in the absence of specific anti-CMV therapy. This response correlated with protection against CMV retinitis in a group of patients at high risk of development of disease. These results help to explain why the natural history of CMV disease has altered since the introduction of such therapeutic regimens.
AIDS-Related Opportunistic Infections↗