Biomedical subjects
Publications and source records attributed to P Jones.
We performed a randomised controlled crossover trial of clinic letters. Structured letters were compared with conventional letters containing problem lists. There were 32 participants; 25 preferred the structured letter. Median rating and items identified were higher for the structured letter. Structured clinical correspondence with paragraph headings is strongly preferred and increases comprehension.
STUDY OBJECTIVE: To develop a cross disciplinary literature search methodology for conducting systematic reviews of all types of research investigating aspects of the built environment and the health of the public. DESIGN: The method was developed following a comprehensive search of literature in the area of housing and injuries, using 30 databases covering many disciplines including medicine, social science, architecture, science, engineering, environment, planning and psychology. The results of the database searches, including the type (or evidence) of research papers identified, were analysed to identify the most productive databases and improve the efficiency of the strategy. The revised strategy for literature searching was then applied to the area of neighbourhoods and mental health, and an analysis of the evidence type of references was carried out. In recognition of the large number and variety of observational studies, an expanded evidence type classification was developed for this purpose. MAIN RESULTS: From an analysis of 722 citations obtained by a housing and injuries search, an overlap of only 9% was found between medical and social science databases and only 1% between medical and built environment databases. A preliminary evidence type classification of those citations that could be assessed (from information in the abstracts and titles) suggested that the majority of intervention studies on housing and injuries are likely to be found in the medical and social science databases. A number of relevant observational studies (10% of all research studies) would have been missed, however, by excluding built environment and grey literature databases. In an area lacking in interventional research (housing/neighbourhoods and mental health) as many as 25% of all research studies would have been missed by ignoring the built environment and grey literature. CONCLUSIONS: When planning a systematic review of all types of evidence in a topic relating to the built environment and the health of the public, a range of bibliographical databases from various disciplines should be considered.
In North Staffordshire, the Achieving Sustainable Quality in Maternity (ASQUAM) meetings provide the programme for clinical guidelines and audit over the following year. The ASQUAM clinical effectiveness programme has attempted to address a number of the issues identified as obstacles to informed democratic prioritization. For example, it became clear that a number of topics raised were actually research questions. The organizers therefore decided to split the fourth ASQUAM day into an 'audit' morning and a 'research' afternoon. The meeting organized by RJ, CR and PJ in partnership with the Midwives Information and Resource Service and the National Childbirth Trust, was timed to allow the research ideas to feed into the national Health Technology Assessment (HTA) programme. This meeting was designed to increase the profile of ASQUAM amongst consumers and to increase their representation at the meeting. Objectives were to choose a new set of research priorities for the year 2000, and to ascertain the voting pattern of comparison to health professionals. There was overall agreement in terms of priorities, with the consumer group prioritizing 8 of the 10 topics chosen by the professionals (or 10 of the 11). No significant differences between the proportions of voted cast for each topic by professionals and consumers were found apart from topic 20. The numbers of consumers were small which does limit the number the validity of statistical comparisons. Nevertheless, it is clear that voting patterns were similar. Overall the process suggests that democratic prioritization is a viable option and one that may become essential within the framework of clinical and research governance.
OBJECTIVE: To evaluate the effectiveness of an intervention package to promote external cephalic version (ECV). STUDY DESIGN: (1) Design and Setting--A randomised-controlled trial of 20 consultant-based maternity units in the West Midlands NHS Region. (2) Intervention Units--One consultant obstetrician from each unit was encouraged to promote changes in clinical practice within their unit. A multifaceted package including a workshop, written material, guidelines and videos was delivered to these consultants. (3) Control Units--No intervention. (4) Main Outcome Measure--The percentage of women with breech presentation at term who were offered ECV in the antenatal clinic, before and after the intervention. RESULTS: Pre-intervention, there was no difference between the intervention and control units in the proportion of women offered ECV (20 and 19%, respectively). Post-intervention, the proportions were 15% in the control group and 36% in the intervention group (P=0.016). CONCLUSION: This type of intervention package can alter clinical practice and increase the proportion of women with breech presentation at term being offered ECV after the intervention.
OBJECTIVE: To evaluate the efficacy of progesterone and progestogens in the management of premenstrual syndrome. DESIGN: Systematic review of published randomised, placebo controlled trials. STUDIES REVIEWED: 10 trials of progesterone therapy (531 women) and four trials of progestogen therapy (378 women). MAIN OUTCOME MEASURES: Proportion of women whose symptoms showed improvement with progesterone preparations (suppositories and oral micronised). Proportion of women whose symptoms showed improvement with progestogens. Secondary analysis of efficacy of progesterone and progestogens in managing physical and behavioural symptoms. RESULTS: Overall standardised mean difference for all trials that assessed efficacy of progesterone (by both routes of administration) was -0.028 (95% confidence interval -0.017 to -0.040). The odds ratio was 1.05 (1.03 to 1.08) in favour of progesterone, indicating no clinically important difference between progesterone and placebo. For progestogens the overall standardised mean was -0.036 (-0.014 to -0.060), which corresponds to an odds ratio of 1.07 (1.03 to 1.11) showing a statistically, but not clinically, significant improvement for women taking progestogens. CONCLUSION: The evidence from these meta-analyses does not support the use of progesterone or progestogens in the management of premenstrual syndrome.
This 6-week Prospective, Randomized, Open-label Blinded End point (PROBE) study conducted at 12 sites in the United States compared the efficacy and safety of atorvastatin with cerivastatin. In all, 215 hypercholesterolemic patients (low-density lipoprotein [LDL] cholesterol > or = 160 mg/dl [4.14 mmol/L]; triglycerides < or = 400 mg/dl [4.52 mmol/L]) were randomized to receive either atorvastatin 10 mg once daily (n = 108) or cerivastatin 0.3 mg once daily (n = 107). Efficacy was assessed by measuring changes from baseline in LDL cholesterol, total cholesterol, high-density lipoprotein cholesterol, apolipoprotein B, and triglycerides. Atorvastatin produced significantly greater (p < 0.0001) reductions from baseline to week 6 in LDL cholesterol (37.7% vs 30.2%), total cholesterol (27.5% vs 22.2%), and apolipoprotein B (28.6% vs 21.2%), and a significantly greater (p < 0.05) increase from baseline to week 6 in high-density lipoprotein cholesterol (6.8% vs 4.3%) than cerivastatin. Atorvastatin treatment was also associated with a greater percent decrease from baseline to week 6 in triglycerides, with a trend toward statistical significance (p = 0.0982). The percentage of patients that achieved the National Cholesterol Education Program LDL cholesterol goal was greater for those receiving atorvastatin (73%) than for those receiving cerivastatin (66%). The proportion of patients experiencing drug-attributable adverse events, which were mostly mild to moderate and related to the digestive system, was significantly less (p < 0.05) with atorvastatin (5%) than with cerivastatin (14%) treatment. In conclusion, atorvastatin (10 mg/day) is more effective at lowering LDL cholesterol in hypercholesterolemic patients than cerivastatin (0.3 mg/day). Both atorvastatin and cerivastatin are well tolerated, with safety profiles similar to other members of the statin class.
High-performance chelation ion chromatography, using a neutral polystyrene substrate dynamically loaded with 0.1 mM dipicolinic acid, coupled with sector-field inductively coupled plasma mass spectrometry has been successfully used for the separation of the actinides thorium, uranium, americium, neptunium and plutonium. Using this column it was possible to separate the various actinides from each other and from a complex sample matrix. In particular, it was possible to separate plutonium and uranium to facilitate the detection of the former free of spectral interference. The column also exhibited some selectivity for different oxidation states of Np, Pu and U. Two oxidation states each for plutonium and neptunium were found, tentatively identified as Np(V) and Pu(III) eluting at the solvent front, and Np(IV) and Pu(IV) eluting much later. Detection limits were 12, 8, and 4 fg for 237Np, 239Pu, and 241Am, respectively, for a 0.5 ml injection. The system was successfully used for the determination of 239Pu in NIST 4251 Human Lung and 4353 Rocky Flats Soil, with results of 570+/-29 and 2939+/-226 fg g(-1), respectively, compared with a certified range of 227-951 fg g(-1) for the former and a value of 3307+/-248 fg g(-1) for the latter.
Excited states in (216)Th were investigated via prompt and delayed gamma decays and the recoil-decay tagging method. The decay schemes of the I(pi) = (8+), t(1/2) = 128(8) micros, the I(pi) = (11-), t(1/2) = 615(55) ns, and the I(pi) = (14+), t(1/2) > or = 130 ns isomers were established. The configuration pi h(9/2)f(7/2) is assigned to the I(pi) = (8+) isomer, which implies that the h(9/2) and f(7/2) states are nearly degenerate. This is ascribed to increased binding of the f(7/2) orbital by its coupling to a low-lying I(pi) = (3-) state at E(x) = 1687 keV. The role of octupole and pairing correlations for a Z = 92 shell closure prediction is discussed on the basis of shell model calculations.
CONTEXT: The World Health Organization and the United Nations Children's Fund strongly discourage use of pacifiers because of their perceived interference with breastfeeding. Observational studies have reported a strong association between pacifier use and early weaning, but such studies are unable to determine whether the association is causal. OBJECTIVES: To test whether regular pacifier use is causally related to weaning by 3 months postpartum and to examine differences in results according to randomized intervention allocation vs observational use or nonuse of pacifiers. DESIGN: Double-blind, randomized controlled trial conducted from January 1998 to August 1999. SETTING: Postpartum unit of a university teaching hospital in Montreal, Quebec. PARTICIPANTS: A total of 281 healthy, breastfeeding women and their healthy, term singleton infants. INTERVENTIONS: Participants were randomly allocated to 1 of 2 counseling interventions provided by a research nurse trained in location counseling. The experimental intervention (n = 140) differed from the control (n = 141) by recommending avoidance of pacifier use and suggesting alternative ways to comfort a crying or fussing infant. MAIN OUTCOME MEASURES: Early weaning, defined as weaning within the first 3 months, compared between groups; 24-hour infant behavior logs detailing frequency and duration of crying, fussing, and pacifier use at 4, 6, and 9 weeks. RESULTS: A total of 258 mother-infant pairs (91.8%) completed follow-up. The experimental intervention increased total avoidance of pacifier use (38.6% vs 16.0% in the control group), reduced daily use (40.8% vs 55.7%), and decreased the mean number of pacifier insertions per day (0.8 vs 2.4 at 4 weeks [P<.001]; 0.8 vs 3.0 at 6 weeks [P<.001]; and 1.3 vs 3.0 at 9 weeks [P =.004]). In the analysis based on randomized intervention allocation, the experimental intervention had no discernible effect on weaning at 3 months (18.9% vs 18.3% in the experimental vs control group; relative risk [RR], 1.0; 95% confidence interval [CI], 0.6-1.7), and no effect was observed on cry/fuss behavior (in the experimental vs control groups, respectively, total daily duration, 143 vs 151 minutes at 4 weeks [P =.49]; 128 vs 131 minutes at 6 weeks [P =.81]; and 110 vs 104 minutes at 9 weeks [P =.58]). When randomized allocation was ignored, however, we observed a strong observational association between exposure to daily pacifier use and weaning by 3 months (25.0% vs 12.9% of the exposed vs unexposed groups; RR, 1.9; 95% CI, 1.1-3.3). CONCLUSIONS: We found a strong observational association between pacifier use and early weaning. No such association was observed, however, when our data were analyzed by randomized allocation, strongly suggesting that pacifier use is a marker of breastfeeding difficulties or reduced motivation to breastfeed, rather than a true cause of early weaning.
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The urokinase plasminogen activator receptor (uPAR) focuses extracellular protease activity to the cell surface, modulates cell adhesion and activates intracellular signal transduction pathways. In a range of cancers uPAR expression often has a negative correlation with prognosis. Here we show that uPAR transcription is stimulated by V12 H-Ras, the effector loop mutant V12 H-Ras G37 and constitutively-active RalA 72L. RalA-dependent transcription required the presence of the ATF2-like AP1-site at -70 bp and the c-Jun binding motif at -184 bp in the uPAR promoter. Consistent with this, both Gal4-c-Jun- and Gal4-ATF2-fusion proteins were activated by RalA signalling through phosphorylation of their activation domains at Ser63 and Ser73 of c-Jun or Thr69 and Thr71 of ATF2. A transdominant inhibitory mutant of c-Jun N-terminal kinase (JNK) failed to inhibit uPAR transcription demonstrating that JNK activation is not a prerequisite for RalA-dependent uPAR transcription. A dominant negative inhibitor of c-Src effectively inhibited RalA-dependent uPAR transcription identifying it as a downstream effector in the RalA signalling pathway. These data provide evidence for the existence of a novel signalling pathway that links RalA to the activation of uPAR transcription via a c-Src intermediate and activation of AP1.
A water molecule is coproduced with the Compound I intermediate in the reactions of native heme peroxidases and catalases with hydrogen peroxide. As a result of water release/rebinding from/to the coproduct formation site the Compound I intermediate may exist in two forms: a "wet" form, Compound I(H(2)O), in which a water molecule is present at or near the site of coproduct water formation, and Compound I, in which the coproduct water formation site is "dry." It is postulated that the absence or presence of a water molecule at this site provides the structural basis for a redox pathway switching mechanism, such that the transition states for 2-electron equivalent reduction of Compound I intermediates are accessible in the dry form, but that in the wet form only 1-electron equivalent processes are possible, unless release of water can be stimulated. This concept provides the basis of a general mechanism in which the classical functional distinction between catalases and peroxidases, as well as the more complex behavior observed in halide oxidation and halogenation reactions, appear as particular cases in which variations in the degree of retention of water at the coproduct formation site influence Compound I reactivity.
BACKGROUND: Beclomethasone dipropionate (BDP) is available in a wide range of daily doses for the treatment of long-term asthma. OBJECTIVES: To assess the evidence for a dose response relationship for BDP in the treatment of long-term asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trial register, Cochrane Controlled Trials Register (The Cochrane Library issue 1 1999) and references lists of articles. Authors and Glaxo Wellcome UK were contacted to identify eligible studies. We also hand searched the proceeding from relevant respiratory society meetings, the British Journal of Clinical Research and the European Journal of Clinical Research for studies. SELECTION CRITERIA: Prospective, randomised trials comparing two or more daily doses of BDP in patients over the age of two years with long-term asthma. DATA COLLECTION AND ANALYSIS: Trials were selected for inclusion and scored for quality by two reviewers. Data were extracted by one reviewer. Authors were contacted to clarify details of study design and retrieve missing data. MAIN RESULTS: 11 trials involving 1614 subjects were included. Methodological quality was variable. Studies rarely gave a clear indication of the degree of asthma control at baseline. Less than two-fold to five-fold dose differences were assessed by different studies. The results are reported as weighted mean differences (WMD) with 95% confidence limits (95% CI). The number of trials (N) contributing to each outcome is stated. In non-oral steroid treated asthmatics a small advantage of BDP 800 mcg/d over 400 mcg/d was apparent for improvement in morning peak expiratory flow rate (PEFR) compared to baseline, WMD 11 L/min (95% CI 4 to 19 L/min) N=2; improvement in forced expired volume in one second (FEV1) compared to baseline, WMD 9 ml (95% CI 3 to 140) N=1; and reduction in night-time symptom score compared to baseline, WMD 0.13 (95% CI 0.04 to 0.22) N=1. Studies that assessed BDP 1000 v 500 mcg/d and BDP 1600 v 400 mcg/d demonstrated significant advantage of higher dose over lower dose for histamine bronchial hyper-responsiveness (BHR) and percentage improvement in FEV1 compared to baseline. No differences between higher and lower daily doses of BDP were apparent for daytime symptoms, withdrawals due to asthma exacerbation, oropharyngeal side effects or measures of hypothalamo-pituitary-adrenal (HPA) function. No difference in prednisolone sparing effect was apparent when comparing high dose and low dose BDP in oral corticosteroid (OCS) dependent patients. REVIEWER'S CONCLUSIONS: BDP appears to demonstrate a shallow dose response effect in long-term asthma for a small number of efficacy outcomes over range of daily doses from 400 mcg/d to 1600 mcg/d, although the clinical significance of the improvements afforded by higher doses is questionable.
OBJECTIVE: The aim of this study was to describe the features of cancers of the uterus, ovary, and other uterine adnexae in a large cohort of in vitro fertilization (IVF) patients and to thereby assist gynecologic oncologists in counseling patients with a history of infertility. METHODS: Record-linkage to population-based cancer registries was used to determine the incidence of invasive cancer in a cohort of 29,700 IVF patients. Pathology reports were made available by the cancer registries and reviewed blind to IVF treatment status. Patient information was abstracted from IVF clinic records. RESULTS: Twelve cancers of the uterus and 13 cancers of the ovary and other uterine adnexae were identified and pathology reports were reviewed for all but 1. Patients ranged in age at diagnosis from 28 to 48 years. Five cancers were diagnosed within 8 months of referral for IVF or IVF treatment; the others were diagnosed between 1 and 12 years later. The ovarian cancers were of the following histologic types: serous (4), mucinous (1), seromucinous (1), endometrioid (3), clear cell (2), and unknown type (1). A choriocarcinoma of the fallopian tube was diagnosed in a woman with a history of tubal infertility. Cancers of the uterus included endometrial adenocarcinomas (8), stromal sarcomas (2), and leiomyosarcomas (2). Ovarian cancer was diagnosed in a woman with Bloom's syndrome, a rare autosomal recessive disorder associated with increased cancer risk. CONCLUSION: Cancer cases in this large, well-defined cohort of IVF patients show a broad range of patient and tumor characteristics. We found an increased incidence of uterine sarcoma in women with a history of infertility. Increased ascertainment of preexisting cancers in the course of infertility investigations and management is to be expected.
AIMS/HYPOTHESIS: Sulphonylureas stimulate insulin secretion by closing ATP-sensitive potassium (KATP) channels in the pancreatic beta-cell membrane. KATP channels are also found in other tissues, including heart and smooth muscle, where they link cellular metabolism to electrical activity. The sulphonylurea gliclazide blocks recombinant beta-cell KATP channels (Kir6.2/SUR1) but not heart (Kir6.2/SUR2A) or smooth muscle (Kir6.2/SUR2B) KATP channels with high potency. In this study, we examined the specificity of gliclazide for the native (as opposed to recombinant) KATP channels in beta cells, heart and smooth muscle. METHODS: The action of the drug was studied by whole-cell current recordings of native KATP channels in isolated pancreatic beta-cells and myocytes from heart and smooth muscle. RESULTS: Gliclazide blocked whole-cell beta-cell KATP currents with an IC50 of 184 +/- 30 nmol/l (n = 6-10) but was much less effective in cardiac and smooth muscle (IC50s of 19.5 +/- 5.4 micromol/l (n = 6-12) and 37.9 +/- 1.0 micromol/l (n = 5-10), respectively). In all three tissues, the action of the drug on whole-cell KATP currents was rapidly reversible. In inside-out patches on beta-cells, gliclazide (1 micromol/l) produced a maximum of 66 +/- 13 % inhibition (n = 5), compared with more than 98 % block in the whole-cell configuration. CONCLUSION/INTERPRETATION: Gliclazide is a high-potency sulphonylurea which shows specificity for the pancreatic beta-cell KATP channel over heart and smooth muscle. In this respect, it differs from glibenclamide. The difference in the maximal block observed in the excised patch and whole-cell recordings from beta-cells, may be due to the absence of intracellular Mg-nucleotides in the excised patch experiments.
Plants are exposed to a wide range of toxic and bioactive low-molecular-weight molecules from both exogenous and endogenous sources. Glycosylation is one of the primary sedative mechanisms that plants utilise in order to maintain metabolic homeostasis. Recently, a range of glycosyltransferases has been characterized in detail with regard to substrate specificity. The next step in increasing our understanding of the biology of glycosylation will require information regarding the exact role of individual glycosyltransferases in planta, as well as an insight into their potential involvement in metabolon-complexes. Hopefully, this will answer how a large number of glycosyltransferases with broad, rather than narrow, substrate specificity can be constrained in order to avoid interfering with other pathways of primary and secondary metabolism. These and other topics are discussed.
Large quantities of diverse polar organic chemicals are routinely discharged from oil production platforms in so-called produced waters. The environmental fate of many of these is unknown since few methods exist for their characterisation. Preliminary investigations into the use of multistage electrospray ionisation ion trap mass spectrometry (ESI-MSn) show its potential for the identification and quantification of compounds in specialty oilfield chemicals (corrosion inhibitors, scale inhibitors, biocides and demulsifiers) and produced waters. Multiple stage mass spectrometry (MSn) with both positive and negative ion detection allows high specificity detection and characterisation of a wide range of polar and charged molecules. For example, linear alkylbenzenesulfonates (LAS), alkyldimethylbenzylammonium compounds, 2-alkyl-1-ethylamine-2-imidazolines, 2-alkyl-1-[N-ethylalkylamide]-2-imidazolines and a di-[alkyldimethylammonium-ethyl]ether were all identified and characterised in commercial formulations and/or North Sea oilfield produced waters. The technique should allow the marine environmental effects and fates of some of these polar compounds to be studied.
The AML1 (CBFA2) gene is the most frequent target of chromosomal rearrangements observed in human acute leukemia. These rearrangements include the commonly reported t(8;21)(q22;q22) or AML1/ETO fusion in AML-M2, the t(3;21)(q26;q22) or AML1 fusion with one of three genes, MDS1, EAP or EVI1, in therapy-related AML and MDS, as well as in blast crisis in CML and the t(12;21)(p13;q22) or TEL/AML1 fusion in B-cell ALL. In addition to the t(3;21), other AML1 translocations have also been reported in therapy-related MDS and AML, particularly after treatment with topoisomerase II inhibitors. AML1 gene rearrangements have also been observed less frequently with numerous other chromosomal partners. Here, we describe a patient with AML-M4 and a previously unreported rearrangement involving the AML1 locus and an unknown locus on the short arm of chromosome 1 at 1p32.