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S Fielding

Publications and source records attributed to S Fielding.

At least 19 recordsLinked to original sources
PubMed2006

Methods for handling missing data in palliative care research.

Missing data is a common problem in palliative care research due to the special characteristics (deteriorating condition, fatigue and cachexia) of the population. Using data from a palliative study, we illustrate the problems that missing data can cause and show some approaches for dealing with it. Reasons for missing data and ways to deal with missing data (including complete case analysis, imputation and modelling procedures) are explored. Possible mechanisms behind the missing data are: missing completely at random, missing at random or missing not at random. In the example study, data are shown to be missing at random. Imputation of missing data is commonly used (including last value carried forward, regression procedures and simple mean). Imputation affects subsequent summary statistics and analyses, and can have a substantial impact on estimated group means and standard deviations. The choice of imputation method should be carried out with caution and the effects reported.

Adult↗
PubMed2006

Systematic review of the effectiveness and cost-effectiveness of HealOzone for the treatment of occlusal pit/fissure caries and root caries.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of HealOzone (CurOzone USA Inc., Ontario, Canada) for the management of pit and fissure caries, and root caries. The complete HealOzone procedure involves the direct application of ozone gas to the caries lesion on the tooth surface, the use of a remineralising solution immediately after application of ozone and the supply of a 'patient kit', which consists of toothpaste, oral rinse and oral spray all containing fluoride. DATA SOURCES: Electronic databases up to May 2004 (except Conference Papers Index, which were searched up to May 2002). REVIEW METHODS: A systematic review of the effectiveness of HealOzone for the management of tooth decay was carried out. A systematic review of existing economic evaluations of ozone for dental caries was also planned but no suitable studies were identified. The economic evaluation included in the industry submission was critically appraised and summarised. A Markov model was constructed to explore possible cost-effectiveness aspects of HealOzone in addition to current management of dental caries. RESULTS: Five full-text reports and five studies published as abstracts met the inclusion criteria. The five full-text reports consisted of two randomised controlled trials (RCTs) assessing the use of HealOzone for the management of primary root caries and two doctoral theses of three unpublished randomised trials assessing the use of HealOzone for the management of occlusal caries. Of the abstracts, four assessed the effects of HealOzone for the management of occlusal caries and one the effects of HealOzone for the management of root caries. Overall, the quality of the studies was modest, with many important methodological aspects not reported (e.g. concealment of allocation, blinding procedures, compliance of patients with home treatment). In particular, there were some concerns about the choice of statistical analyses. In most of the full-text studies analyses were undertaken at lesion level, ignoring the clustering of lesions within patients. The nature of the methodological concerns was sufficient to raise doubts about the validity of the included studies' findings. A quantitative synthesis of results was deemed inappropriate. On the whole, there is not enough evidence from published RCTs on which to judge the effectiveness of ozone for the management of both occlusal and root caries. The perspective adopted for the study was that of the NHS and Personal Social Services. The analysis, carried out over a 5-year period, indicated that treatment using current management plus HealOzone cost more than current management alone for non-cavitated pit and fissure caries (40.49 pounds versus 24.78 pounds), but cost less for non-cavitated root caries ( 14.63 pounds versus 21.45 pounds). Given the limitations of the calculations these figures should be regarded as illustrative, not definitive. It was not possible to measure health benefits in terms of quality-adjusted life-years, due to uncertainties around the evidence of clinical effectiveness, and to the fact that the adverse events avoided are transient (e.g. pain from injection of local anaesthetic, fear of the drill). One-way sensitivity analysis was applied to the model. However, owing to the limitations of the economic analysis, this should be regarded as merely speculative. For non-cavitated pit and fissure caries, the HealOzone option was always more expensive than current management when the probability of cure using the HealOzone option was 70% or lower. For non-cavitated root caries the costs of the HealOzone comparator were lower than those of current management only when cure rates from HealOzone were at least 80%. The costs of current management were higher than those of the HealOzone option when the cure rate for current management was 40% or lower. One-way sensitivity analysis was also performed using similar NHS Statement of Dental Remuneration codes to those that are used in the industry submission. This did not alter the results for non-cavitated pit fissure caries as the discounted net present value of current management remained lower than that of the HealOzone comparator ( 22.65 pounds versus 33.39 pounds). CONCLUSIONS: Any treatment that preserves teeth and avoids fillings is welcome. However, the current evidence base for HealOzone is insufficient to conclude that it is a cost-effective addition to the management and treatment of occlusal and root caries. To make a decision on whether HealOzone is a cost-effective alternative to current preventive methods for the management of dental caries, further research into its clinical effectiveness is required. Independent RCTs of the effectiveness and cost-effectiveness of HealOzone for the management of occlusal caries and root caries need to be properly conducted with adequate design, outcome measures and methods for statistical analyses.

Adolescent↗
PubMed2000

Timing of pain and bleeding after mifepristone-induced abortion.

Previous studies of medical abortion with mifepristone and a prostaglandin have reported percentages of subjects who experience cramping and/or bleeding relative to prostaglandin use. This is the first analysis of cramping and bleeding onset patterns in subjects treated with low-dose (200 mg) mifepristone and 800 microg vaginal misoprostol at 24, 48, or 72 h after mifepristone. We analyzed the cramping and bleeding onset patterns in subjects up to 8 weeks pregnant who used 800 microg vaginal misoprostol at 24, 48, or 72 h after 200 mg of oral mifepristone. We collected data from subjects' symptom diaries and divided symptom onset into 3 categories: before misoprostol use, 0--12 h following misoprostol, and more than 12 h after misoprostol. Of the 2,302 subjects, cramping and bleeding onset data were available for 2,030 (88%) and 2,123 (92%), respectively. Across all groups, 230 (11%) experienced cramping and 445 (21%) experienced bleeding before misoprostol use. There was a significantly higher percentage of subjects who experienced early cramping and/or early bleeding between the three treatment groups, and this was related to the interval between mifepristone and misoprostol. In the 12 h following misoprostol administration, cramping and bleeding patterns were similar in the three groups. The longer subjects waited to insert misoprostol, the more likely they were to experience early cramping and/or bleeding. After misoprostol insertion, cramping and bleeding patterns are similar regardless of treatment group. Patients and providers cannot rely on symptom onset to predict treatment success.

Abortifacient Agents, Nonsteroidal↗
PubMed1998

Impact of nasal ventilation on survival in hypercapnic Duchenne muscular dystrophy.

BACKGROUND: Respiratory failure is the commonest cause of death in patients with Duchenne muscular dystrophy (DMD). Life expectancy is less than one year once diurnal hypercapnia develops. This study examines the effects of nasal intermittent positive pressure ventilation (NIPPV) on survival in symptomatic Duchenne patients with established ventilatory failure. METHODS: Nocturnal NIPPV was applied in 23 consecutive patients with DMD of mean (SD) age 20.3 (3.4) years who presented with diurnal and nocturnal hypercapnia. RESULTS: One year and five year survival rates were 85% (95% CI 69 to 100) and 73% (95% CI 53 to 94), respectively. Early changes in arterial blood gas tensions following NIPPV occurred with mean (SD) PO2 increasing from 7.6 (2.1) kPa to 10.8 (1.3) kPa and mean (SD) PCO2 falling from 10.3 (4.5) kPa to 6.1 (1.0) kPa. Improvements in arterial blood gas tensions were maintained over five years. Health perception and social aspects of SF-36 health related quality of life index were reported as equivalent to other groups with nonprogressive disorders using NIPPV. CONCLUSIONS: Nasal ventilation is likely to increase survival in hypercapnic patients with Duchenne muscular dystrophy and should be considered as a treatment option when ventilatory failure develops.

Adolescent↗
PubMed1997

A comparison of the cytology of endomyocardial biopsy washings from heart transplants with biopsy histologic study and peripheral blood lymphocyte counts.

Cytospin preparations of endomyocardial biopsy washings were examined on 117 occasions from 13 heart transplant recipients and categorized according to the pattern of cell types observed. Twenty-nine percent of samples were acellular, a further 10% too bloodstained for analysis, and 61% were cellular. Eight lymphocytic samples were found and in all cases there was at least grade 1B rejection (four grade 1B, three grade 2, and one grade 3A) on histologic study. However, histologic study showed at least 1B rejection in 48% of cases when cytospins showed mixed inflammatory cells, 33% of cases when cytospins were histiocytic and in 35% when cytospins were bloodstained or acellular. Furthermore 16 of these rejection episodes with nonlymphocytic cytospins were grade 2. Although the recovery of a lymphocytic cytospin was specific for rejection, the sensitivity of the test was poor. Even when the sample is adequate, this method of biopsy washings will predict only one third of cases of significant acute rejection (grade 2 or worse). The large proportion of unsuitable samples also severely limits the utility of endomyocardial biopsy washings for the diagnosis of rejection. Histiocytic cytospins were seen in 63% of samples when previous biopsy sites were reported on histologic study and also in all three samples when histologic study showed ischemic injury. A mixed inflammatory cell pattern was seen to a lesser extent (31% of samples) in relation to previous biopsy sites. High peripheral blood lymphocyte counts were found when endomyocardial biopsy washings were lymphocytic or mixed inflammatory and also when histologic study showed endocardial lymphocytic infiltration (Quilty effect).

Biopsy↗
PubMed1995

Bone marrow and serum connective tissue polypeptides in idiopathic myelofibrosis.

The distribution of collagen type VI and tenascin has been determined in both normal and myelofibrotic bone marrow by immunohistological techniques. In normal sections positivity was demonstrated in the periosteum (collagen type VI and tenascin) and in the walls of small blood vessels (tenascin). In contrast, myelofibrotic bone marrow showed an increased deposition of both proteins, especially collagen type VI, although this increase was restricted to the later fibrotic stages of the disease. Serum concentrations of collagen type I (PICP), collagen type III (PIIIP) and laminin (laminin P1) related polypeptides were determined in a further 26 patients. PIIIP levels were significantly raised, in contrast to PICP and laminin P1 concentrations. All three markers, however, were significantly elevated in patients with active/transforming disease. Laminin P1 and PICP levels showed a strong correlation, indicating a relationship between basement membrane and interstitial collagen metabolism, although they do not appear to offer any advantage over PIIIP for the monitoring of disease activity.

Aged↗
PubMed1994

Enhancement of salt intake by choline chloride.

The ingestion of salt (NaCl) in most societies far exceeds levels that are considered necessary and safe. To reduce salt intake, a rat model of salt taste acceptance was created to identify novel, more palatable salt substitutes/enhancers. To induce salt craving, male Sprague-Dawley rats were placed on a low-salt diet and injected weekly (SC) with either 100 mg/kg of deoxycorticosterone acetate (DOCA) or its vehicle, peanut oil. Following 16 h of fluid deprivation, intake was evaluated in a one-bottle acceptance procedure. The DOCA-injected animals consumed large volumes of salt-containing solutions (up to 120 ml in 2 h) and showed sensitivity to and specificity for the salt taste (generally lacking acceptance of dextrose, KCl, ammonium chloride, and water solutions). Using this model, choline chloride was identified as having salt taste-enhancing properties. Choline chloride (0.1-0.7%) significantly enhanced the intake of a dilute salt solution (0.1%). The relevance of the rat model was demonstrated in human taste trials; choline chloride enhanced the palatability of and preference for foods containing this compound. The results of the present experiments support the use of this animal model for evaluating compounds for salt-like taste qualities and suggest that choline chloride will be an effective salt taste enhancer in man.

Animals↗
PubMed1992

Cardiotonic and coronary vasodilator responses to milrinone, forskolin, and analog P87-7692 in the anesthetized dog.

Forskolin and milrinone both increase cyclic AMP concentrations to enhance cardiac contractility and cause vascular dilation in vitro and in vivo. However, forskolin acts via direct stimulation of adenylate cyclase while milrinone inhibits phosphodiesterase (PDE-III) activity. The forskolin analog, 7-desacetyl-7-(O-propionyl)-hydroxyl-aminocarbonyl-forskolin (P87-7692) has also been shown to directly stimulate adenylate cylase and increase cyclic AMP production in isolated cardiac tissue; however, the in vivo activity of this compound has not been described. Thus, the purpose of this study was to compare the cardiovascular effects of equivalent doses of these compounds and to further characterize the cardiotonic activity of P87-7692 in the anesthetized dog. It was found that both i.v. (3-30 micrograms/kg) and intracoronary (0.1-30 micrograms) administration of milrinone, forskolin, and P87-7692 caused dose-related positive inotropic, coronary, and peripheral vasodilator effects in anesthetized dogs; however, P87-7692 produced significantly greater and more sustained cardiotonic activity following a single 30-micrograms/kg, i.v., bolus injection when compared to the same dose of milrinone and forskolin. Analysis of the dose-response relationship between the changes in contractile force and heart rate for these compounds revealed that a 50% augmentation in contractile force was associated with increases in heart rate of 2.1% for milrinone, 6.4% for P87-7692, and 13.7% for forskolin. These data indicate an improved separation between the chronotropic and inotropic effects for P87-7692 as compared to forskolin. All three compounds also produced coronary vasodilation in vivo and in vitro; however, P87-7692 consistently showed greater activity relative to the same doses of milrinone and forskolin. Moreover, P87-7692 was significantly (p less than 0.05) more potent at relaxing KC1-precontracted canine coronary rings, with an EC50 of 2.1 x 10(-7) M as compared to 1.1 x 10(-6) M for forskolin and 3.2 x 10(-6) M for milrinone. The results of these studies indicate that structural modification of the forskolin molecule can increase the separation between positive inotropic and chronotropic effects, improve the overall hemodynamic profile, and prolong the duration of cardiotonic activity for this class of compounds.

Adenylyl Cyclases↗
PubMed1991

GABAmimetic agents display anxiolytic-like effects in the social interaction and elevated plus maze procedures.

Benzodiazepine (BZD) anxiolytics, through their activation of the BZD-GABA receptor complex, display robust anxiolytic-like effects following systemic administration in both conditioned and non-conditioned behavioral procedures. The present results show that the GABAA agonists muscimol (0.5-1.0 mg/kg), THIP (2.5-10.0 mg/kg), and isoguvacine (25.0 mg/kg) as well as the GABA transaminase (GABA-T) inhibitor AOAA (aminooxyacetic acid; 5.0-20.0 mg/kg) following intraperitoneal administration exert anxiolytic-like activity of similar magnitude to that of diazepam in two non-conditioned procedures, namely the social interaction and the elevated plus maze tests. We have also extended our original findings that the anti-epileptic drug sodium valproate exerts an anxiolytic-like effect in the Geller conflict paradigm, to show this agent's robust activity in the social interaction and elevated plus maze tests following systemic administration (100-400 mg/kg). These results show that GABAergic agents that facilitate GABA transmission are effective following systemic administration in non-conditioned anxiety procedures and may indicate potential therapeutic efficacy in certain anxiety states.

Aminooxyacetic Acid↗
PubMed1990

Preclinical anxiolytic profiles of 7189 and 8319, novel non-competitive NMDA antagonists.

Antagonists at excitatory amino acid receptors, especially the N-methyl-d-aspartate (NMDA) subtype, have been shown to possess anticonvulsant and anxiolytic properties (Clineschmidt et al., 1982; Croucher et al., 1982; Bennett and Amrick, 1986). 7189 and 8319, two closely related benzeneethanamines, are potential novel anxiolytic agents which bind with high affinity to the NMDA receptor at the non-competitive site and are relatively non-toxic (LD50's-160 mg/kg, ip). 7189 and 8319 showed anxiolytic effects in schedule controlled conflict assays as well as in the social interaction (SI) and elevated plus maze (EPM) procedures in rats. Following intraperitoneal administration of 7189 at 20 to 60 mg/kg, conflict responding was increased from 2- to 7-fold in the modified Cook and Davidson and Geller conflict paradigms. 8319, at 2.5 to 5 mg/kg, produced a two fold increase in conflict responding. In the non-schedule controlled procedures, 7189 at 20 mg/kg increased SI time by 23% while in the EPM at 10 to 20 mg/kg, open arm exploration time increased by 41 to 77%. Likewise, 8319 at 2.5 and 5 mg/kg increased open arm exploration and SI time by 50 and 37%, respectively. In summary, 7189 and 8319 were efficacious in four behavioral procedures predictive of potential anxiolytic agents. Although these compounds have not been submitted for clinical evaluation, they may represent a new class of beneficial compounds for the treatment of anxiety.

Aniline Compounds↗
PubMed1990

Preclinical anticonvulsant and neuroprotective profile of 8319, a non-competitive NMDA antagonist.

8319, ((+-)-2-Amino-N-ethyl-alpha-(3-methyl-2-thienyl)benzeneethanamine 2HCl), is a novel compound with the profile of a non-competitive NMDA antagonist. The compound displaced [3H] TCP with high affinity (IC50 = 43 nM), but was inactive at the NMDA, benzodiazepine and GABA sites; in vivo, 8319 showed good efficacy as an anticonvulsant and potential neuroprotective agent. It blocked seizures induced by NMDLA, supramaximal electroshock, pentylenetetrazol (PTZ), picrotoxin, and thiosemicarbazide with ED50's of 1-20 mg/kg ip. As a neuroprotective agent, 8319 (30-100 mg/kg sc) prevented the death of dorsal hippocampal pyramidal cells induced by direct injection of 20 nmol NMDA. At 15 mg/kg ip, the compound was also effective against hippocampal neuronal necrosis induced via bilateral occlusion of the carotid arteries in gerbils. In summary, 8319 is a noncompetitive NMDA antagonist with good anticonvulsant activity and may possess neuroprotective properties useful in the treatment of brain ischemia.

Aniline Compounds↗
PubMed1989

Effects of 5-HT1A receptor agonists and NMDA receptor antagonists in the social interaction test and the elevated plus maze.

The effects of several 5-HT1A agonists and excitatory amino acid antagonists were compared to the standard benzodiazepines, diazepam and chlordiazepoxide (CDP) in two assays predictive of anxiolytic activity, the social interaction and elevated plus maze procedures. Indicative of anxiolytic effects the 5-HT1A agonists, buspirone, gepirone and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) all significantly increased social interaction time and open arm exploration time in the social interaction and elevated plus maze procedures, respectively. Likewise, anxiolytic activity in these assays were also produced by the competitive N-methyl-D-aspartate (NMDA) antagonists, 2-amino-5-phosphonovaleric acid (AP-5), 2-amino-7-phosphonoheptanoic acid (AP-7), 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the non-competitive NMDA antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) while NMDA produced anxiogenic effects. Furthermore, the anxiolytic effects of these agents were of equal magnitude to the benzodiazepines. These two classes of compounds were differentiated in the yohimbine-induced seizure assay, with the NMDA antagonists dose dependently antagonizing seizures similar to the benzodiazepines while the 5-HT1A agonists were inactive. These results suggest that the 5-HT1A agonists and the NMDA antagonists may be potential non-classical anxiolytic agents with different mechanisms of action.

Animals↗
PubMed1989

Mu-opioid component of the ethylketocyclazocine (EKC) discriminative stimulus in the rat.

The opioid receptor selectivity of the EKC discriminative stimulus was characterized in Fischer rats trained to discriminate 0.3 mg/kg EKC (SC) from saline in a two-choice discrete-trial avoidance paradigm. The putative kappa-opioid receptor agonists EKC and U50,488H completely generalized with the EKC cue at doses of 0.3 and 10 mg/kg, respectively. The putative mu-opioid receptor agonists morphine (M) and fentanyl also dose-dependently generalized with the EKC stimulus. The generalization of M with EKC was not symmetrical, EKC and U50,488H produced little or no M-appropriate responding in rats trained to discriminate 3.0 mg/kg M (SC) from saline. This generalization pattern may reflect a lack of opioid receptor selectivity of the EKC stimulus. However, distinct mu-opioid and kappa-opioid components of the EKC cue could be identified using graded doses of naloxone in EKC-trained rats. The discriminative effects of morphine and fentanyl were blocked completely by doses of 0.1-1.0 mg/kg naloxone, whereas doses of naloxone 3-10 times greater were necessary to block the discriminative effects of EKC and U50,488H. These results suggest that EKC produces a complex discriminative stimulus with mu-opioid and kappa-opioid components that can be separated using antagonists such as naloxone.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Studies on the ability of smoke from different types of cigarettes to induce DNA single-strand breaks in cultured human cells.

In this paper we report preliminary studies using alkaline elution to examine the incidence of DNA-strand breakage in human lung cells exposed to smoke/phosphate-buffered saline generated from cigarettes of different tar contents and filter status. The majority of the DNA breaks induced were abolished by catalase indicating a role for active oxygen species. The incidence of breaks did not correlate with the tar content of the cigarettes. The presence of a filter in the cigarette reduced the TPM concentration of the mainstream smoke but did not reduce the number of single-strand breaks occurring in DNA after exposure to smoke/PBS. This last parameter was however reduced if the filter was ventilated.

Catalase↗
PubMed1989

Characterization of the discriminative stimulus effects of physostigmine in the rat.

Rats were trained to discriminate physostigmine (0.1 mg/kg s.c.) from saline in a two-choice, discrete-trial avoidance paradigm. Stimulus generalization curves for physostigmine were steep; complete generalization with physostigmine occurred only at the 0.1 mg/kg training dose. The muscarinic cholinergic agonists oxotremorine, pilocarpine and arecoline were evaluated for physostigmine-like discriminative effects. Oxotremorine generalized with physostigmine at a dose of 0.1 mg/kg in four of six rats tested; partial generalization was engendered by this dose in the remaining two animals. Complete generalization with physostigmine was produced in only one of six rats treated with pilocarpine. However, pilocarpine (3.0-10 mg/kg) did engender some physostigmine-appropriate responding in all rats tested. Arecoline (1.0 mg/kg) produced primarily saline-appropriate responding in all animals tested. Neostigmine, eseroline and nicotine were tested for physostigmine-like discriminative effects in order to assess the specificity of the physostigmine cue. Eseroline (1.0 mg/kg), an opioid-like derivative of physostigmine, and neostigmine (0.1 mg/kg) engendered saline-appropriate responding. Similarly, nicotine failed to generalize with physostigmine at doses up to 1.0 mg/kg. The discriminative stimulus effects of physostigmine were sensitive to antagonism by atropine. Complete blockade of the stimulus effects of the training dose of physostigmine was produced by 1.0 to 3.0 mg/kg of atropine. In contrast, a 10-fold higher dose of the quaternary antagonist homatropine methylbromide was necessary to block the discriminative effects of physostigmine. The discriminative effects of physostigmine were not blocked or were only partially blocked by mecamylamine at doses up to 10 mg/kg. The results of these experiments suggest that the discriminative stimulus effects of physostigmine are selective and probably centrally mediated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗