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A Bond

Publications and source records attributed to A Bond.

At least 19 recordsLinked to original sources
PubMed2005

Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology.

These British Association for Psychopharmacology guidelines cover the range and aims of treatment for anxiety disorders. They are based explicitly on the available evidence and are presented as recommendations to aid clinical decision making in primary and secondary medical care. They may also serve as a source of information for patients and their carers. The recommendations are presented together with a more detailed review of the available evidence. A consensus meeting involving experts in anxiety disorders reviewed the main subject areas and considered the strength of evidence and its clinical implications. The guidelines were constructed after extensive feedback from participants and interested parties. The strength of supporting evidence for recommendations was rated. The guidelines cover the diagnosis of anxiety disorders and key steps in clinical management, including acute treatment, relapse prevention and approaches for patients who do not respond to first-line treatments.

Adolescent↗
PubMed2004

Homeopathic proving symptoms: result of a local, non-local, or placebo process? A blinded, placebo-controlled pilot study.

BACKGROUND: Homeopathic pathogenetic trials (HPTs) (provings) are the pillar of homeopathy. Symptoms experienced by healthy volunteers are used to find the correct medicine for therapy. It is unclear whether these symptoms are specific or due to placebo noise. Furthermore, it is uncertain whether proving effects, if present at all, are due to a local or non-local process OBJECTIVES: To develop a test model which allows for testing if homeopathic proving symptoms are caused by placebo or causative mechanisms, and if these symptoms are due to local or non-local processes. DESIGN: Randomised, blinded, placebo-controlled, parallel-group study, with 1-week baseline and 2-weeks proving period. SUBJECTS: 11 healthy volunteers from two different homeopathic schools. PROVING SUBSTANCE: An homeopathic medicine (Cantharis 30c), blindly chosen from 12 potential medicines, compared to placebo. OUTCOME MEASURE: Number of symptoms typical for the medicine in the experimental and control group during baseline and proving period. RESULTS: During baseline there was no difference in the number of typical or atypical symptoms in either group. During the proving period, both more typical symptoms for Cantharis (P= 0.03) and more atypical symptoms (P= 0.02) were observed compared to baseline. Between-group differences were not significant. Effect sizes for the difference between the proving and control group for typical symptoms was d=0.4, and for atypical symptoms d=0.6. DISCUSSION: This proving model could be valuable in studying the validity of proving symptoms of homeopathic substances in healthy volunteers. CONCLUSION: Homeopathic proving symptoms appear to be specific to the medicine and do not seem to be due to a local process. Since this was a pilot study using a small number of provers, rival hypotheses cannot be ruled out and the study needs replication.

Adult↗
PubMed2004

cis-Element clustering correlates with dose-dependent pro- and antisignaling effects of IL18.

We examine the effects of IL18 on monocytes by performing microarray experiments using cell line KG1. Based on sensitivity to IL18, we identified three functionally distinct gene expression clusters (EC). We see little proinflammatory gene induction at low IL18 concentrations, but instead observe induction of diverse NF kappa B signaling inhibitors. Conversely, intermediate concentrations of IL18 induced proinflammatory genes including the activating subunits of NF kappa B. At the highest IL18 concentration, we observe a third gene cluster containing the proapoptotic Fas gene among others. Clustering of IL18-responsive genes based on cis-elements in their promoters agreed well with the ECs. We conclude that IL18 produces a dose-dependent transcriptional response that can in part be attributed to the composition of cis-elements in the promoters of IL18-responsive genes. These results also support a model for regulatory mechanisms that prevent spurious immune response due to weak cytokine fluctuations and a separate mechanism enabling induction of proinflammatory functions by higher levels of cytokine.

Cell Line, Tumor↗
PubMed2003

Preconcentration of radium isotopes from natural waters using MnO2 Resin.

We have characterized "MnO2 Resin," a new resin developed by the PG Research Foundation, for radium adsorption over wide ranges of pH, reaction times and salt concentrations. We show that the sorption of 133Ba (used as a proxy for Ra) is highly dependent on pH with the most useful range from pH 4 to 8. The surface layers of the Mn oxides apparently become more positively charged under acidic conditions (below pH 4), which prevents diffusion of positively charged alkaline earth species (e.g. Ba2+, Ra2+) into the sorption sites. Adsorption at higher pH is thought to be inhibited because of carbonate complexation. We found that the sorption characteristics for radium onto MnO2 Resin are especially favorable for low-salinity waters but the sorption is still very satisfactory for highly salted solutions (KD=2.8x10(4) in both cases) but with slower kinetics. For analytical purposes, both column and pump experiments showed high recoveries with no measurable discrimination between Ra and Ba regardless of flow rates in fresh water. Seawater tests showed that recoveries of Ra and Ba are lower than fresh water at elevated flow rates with Ra adsorption higher than Ba at flow rates above 10 ml/min.

Barium Radioisotopes↗
PubMed2003

Deliberate self-harm in Oxford, 1990-2000: a time of change in patient characteristics.

BACKGROUND: Trends in deliberate self-harm (DSH) are important because they have implications for hospital services, may indicate levels of psychopathology in the community and future trends in suicide, and can assist in identification of means of suicide prevention. METHOD: We have investigated trends in DSH and characteristics of DSH patients between 1990 and 2000 based on data collected through the Oxford Monitoring System for Attempted Suicide. RESULTS: During the 11-year study period 8590 individuals presented following 13858 DSH episodes. The annual numbers of persons and episodes increased overall by 36.3% and 63.1% respectively. Rates (Oxford City) declined, however, in the final 3 years. There were gender- and age-specific changes, with a rise in DSH rates in males aged > or = 55 years and in females overall and those aged 15-24 years and 35-54 years. Repetition of DSH increased markedly during the study period. Antidepressant overdoses, especially of SSRIs, increased substantially. Paracetamol overdoses declined towards the end of the study period. Alcohol abuse, use of alcohol in association with DSH, and violence increased, especially in females, and the proportion of patients in current psychiatric care and misusing drugs also rose. CONCLUSIONS: While overall rates of DSH did not increase markedly between 1990 and 2000, substantial changes in the characteristics of the DSH population and a rise in repetition suggest that the challenges facing clinical services in the management of DSH patients have grown.

Adolescent↗
PubMed2001

Improvement of coronary artery endothelial dysfunction with lipid-lowering therapy: heterogeneity of segmental response and correlation with plasma-oxidized low density lipoprotein.

OBJECTIVES: This study assessed coronary artery endothelial function in patients with hypercholesterolemia before and after lipid lowering, using quantitative angiography to examine the acetylcholine (Ach) response along the entire analyzable vessel. BACKGROUND: Lipid lowering reverses endothelial dysfunction, but whether improvement occurs only in some segments and not others has not been established. Statistical correlation of improvement with specific lipid moieties remains undefined. METHODS: Quantitative angiography was performed after Ach (10(-6), 10(-5), 10(-4) M) in 29 patients with coronary atherosclerosis before and 18 +/- 5.2 months after lipid-lowering treatment (statins, bile sequestrant resins). Standard lipid moieties and markers of oxidized low density lipoprotein (LDL) (immunoglobulin G and M autoantibody titers to malondialdehyde-LDL, E06 epitope) were measured serially. RESULTS: Pre-treatment of the vessel diameters at control and with 10(-6)M, 10(-5) M and 10(-4) M Ach were 2.108 +/- 0.085, 2.086 +/- 0.087, 2.069 +/- 0.084 and 1.963 +/- 0.097 mm (M +/- SE), respectively, and increased at follow-up to 2.139 +/- 0.094, 2.119 +/- 0.086, 2.127 +/- 0.084 and 2.080 +/- 0.085 mm (p < 0.0001). Improvement in the most constricted and modest declination in the more dilated segments were observed. Change in the E06 and Apolipoprotein A-1 titers correlated with improved vasomotion (p = 0.027 and 0.005, respectively). The pre- and post-treatment levels of the E06 epitope, as well as the post-treatment IgM autoantibody titer to MDA-low density lipoprotein, also correlated (p < 0.028, < 0.001 and p < 0.004, respectively). CONCLUSIONS: Drug treatment reverses endothelial dysfunction, but the effect is heterogeneous. Most coronary segments show enhancement, while others show declination of dilation, underscoring the importance of assessing the entire analyzable artery. Improvement in vasomotion correlates most significantly with markers of plasma-oxidized low-density lipoprotein.

Acetylcholine↗
PubMed2001

Therapeutic effects of cysteine protease inhibition in allergic lung inflammation: inhibition of allergen-specific T lymphocyte migration.

OBJECTIVE AND DESIGN: We have evaluated the effects of the broad-spectrum cysteine protease inhibitor E64 on allergic lung inflammation in the mouse ovalbumin model of human asthma. We have also characterised membrane-associated cathepsin enzyme activity on a range of cell types. MATERIALS: Balb/C mice, E64 and CA074, various cell lines. TREATMENT: E64 was administered by subcutaneous minipump into ovalbumin-sensitised mice prior to intranasal ovalbumin challenge. The effect of E64 on ovalbumin-induced inflammation in vivo and ovalbumin-specific T cell proliferation in vitro and ex vivo was examined. Membrane-associated cathepsin activity on various cell types was measured. RESULTS: E64 treatment (0.36-0.48 mg/day) led to a significant reduction in eosinophil numbers and lung weights in the mouse model. Histological examination of lungs confirmed the anti-inflammatory effect. E64 greatly reduced ovalbumin-specific T cell numbers in the lymph nodes draining the lung following intranasal challenge whilst an accumulation of these T cells was found in the 'priming' lymph nodes. An analysis of various cells involved in lymphocyte priming and migration revealed that monocytes, dendritic cells and endothelial cells express high levels of membrane-associated cathepsin B activity. CONCLUSIONS: Since E64 is not cell permeable and does not inhibit antigen-induced T cell proliferation in vitro or in vivo, the data indicate that membrane-associated cysteine proteases, possibly cathepsin B, may regulate T lymphocyte migration in vivo.

Allergens↗
PubMed2001

Social class and suicidal behaviour: the associations between social class and the characteristics of deliberate self-harm patients and the treatment they are offered.

BACKGROUND: Rates of deliberate self-harm (DSH) in the United Kingdom are much higher in lower than upper social class groups. Previous investigations have shown differences in socio-demographic and clinical characteristics of male patients according to social class. In two studies of DSH patients in Edinburgh the extent of provision of psychiatric aftercare was inversely related to social class. These findings have not been investigated in other areas. METHOD: Data collected through the Oxford Monitoring System for Attempted Suicide were used to examine the association between social class and socio-demographic and clinical characteristics in male and female DSH patients who presented to the general hospital in Oxford between mid-1988 and 1996 and to determine whether the previously reported social class differences in provision of psychiatric aftercare were replicated. RESULTS: Data on social class were available for 2,828 DSH patients (1,290 males, 1,538 females). In both genders, lower social class group tended to be associated with younger age. In males, the main social class differences were found in under-35-year-olds, in whom lower social class was related to criminal record, violence to others and drug misuse. In females, psychiatric disorders were diagnosed more frequently in the higher social class groups, but only in the under-35 age group. In neither gender was there a significant association between social class and the frequency of offer of psychiatric aftercare following DSH. CONCLUSIONS: There are considerable variations in socio-demographic and clinical characteristics of both male and female DSH patients in different social classes, especially in younger patients. The reason for the absence of a marked social class gradient in psychiatric aftercare found in this study in contrast to the results from previous investigations may be related to differences in styles of service.

Adolescent↗
PubMed2001

Substances used in deliberate self-poisoning 1985-1997: trends and associations with age, gender, repetition and suicide intent.

BACKGROUND: Rates of deliberate self-poisoning have increased in recent years. While over-the-counter availability and prescribing patterns may influence trends in substances used in overdose, these may also be related to clinical characteristics of patients. We investigate trends in substances used for self-poisoning and the influence of age, gender, suicidal intent and repetition status on the substances used. METHOD: Data collected by the Oxford Monitoring System for Attempted Suicide were used to review trends and patterns of self-poisoning between 1985 and 1997. RESULTS: There were substantial increases in self-poisoning with paracetamol and antidepressants. While the increase in antidepressant self-poisoning closely paralleled local prescribing figures during 1995-97, SSRI antidepressant overdoses occurred somewhat more often than expected compared with tricyclic overdoses. Paracetamol overdoses were more common in first-timers and young people, whereas overdoses of antidepressants and tranquillizers were more common in repeaters and older people. Self-poisoning with gas and non-ingestible poisons was associated with high suicidal intent. CONCLUSIONS: There have been marked changes in the substances used for self-poisoning, which seem primarily to reflect availability, as do the influences of age and repeater status on choice of substances used. Degree of suicidal intent may also influence choice of method of self-poisoning.

Acetaminophen↗
PubMed2001

A survey of frequent attenders at a gastroenterology clinic.

OBJECTIVE: To examine a group of patients satisfying criteria for "frequent attending" as part of an audit of an outpatient gastroenterology service, and to note the prevalence of those with no conspicuous organic disease to account for their symptomatology. METHODS: We used the hospital computer (Oxford Patient Administration System, OXPAS) to identify 2530 consecutive patients who were given an appointment to attend the gastroenterology clinic during an 11-month period. Patients designated "frequent attenders" had their notes flagged before the clinic attendance and were examined in more detail. A frequent attender was defined as a patient who had attended any hospital outpatient clinic in the three Oxford general hospitals on four or more occasions in the previous 12 months. The gastroenterologist then interviewed the patients satisfying these criteria and indicated whether he/she was satisfied that there was no relevant organic disease to account for the symptoms. RESULTS: Of the total 2530 patients, 762 (30%) satisfied our criteria for frequent attendance (FA). Of these, 452 (59%) had organic disease, 128 (17%) either did not attend or cancelled and 159 (21%) had no relevant organic disease. The diagnosis was uncertain in 23 patients (3%). Of patients satisfying our criteria for frequent attending, approximately 20-25% had no established gastroenterological disease. CONCLUSIONS: Frequent attenders present formidable management problems for the gastroenterologist. If they can be identified by computer before the outpatient visit then assessment and management might be more appropriately supervised in designated clinics by more experienced gastroenterology staff.

Adolescent↗
PubMed2001

Potentiation of responses to AMPA on central neurones by LY392098 and LY404187 in vivo.

Enhancement of AMPA receptor mediated synaptic excitation has the potential to aid in the treatment of several psychiatric conditions. To test such claims there is a need to develop more potent compounds than those presently available and to demonstrate that they cross the blood-brain barrier to affect responses at central AMPA receptors. We have now completed in vivo tests with two such compounds, the newly discovered biarylpropylsulfonamides, LY392098 and LY404187, on spinal and hippocampal neurones in anaesthetised rats. In the initial study on spinal neurones, LY392098 (30-1000 microg/kg i.v.) dose-dependently increased responses to iontophoretically administered AMPA but not those to NMDA. Subsequently in a more detailed follow-up study on hippocampal neurones, LY392098 (1-100 microg/kg i.v.) and LY404187 (1-100 microg/kg i.v.) enhanced in a dose-dependent manner responses to AMPA. Responses to NMDA were also enhanced but to a less extent. Such enhanced responses to NMDA, but not those to AMPA, were reduced by the NMDA antagonist, ketamine (0.5-1 mg/kg i.v.) whereas the selective AMPA antagonist, LY300168 (GYKI53655; 1 mg/kg i.v.), reduced responses to both NMDA and AMPA. LY392098 also potentiated the synaptic excitation of dentate granule cells following perforant path stimulation. These combined data show that, at doses not dissimilar to those affecting behavioural responses (1-1000 microg/kg; see accompanying papers), the two new drugs cross the blood-brain barrier to affect directly the sensitivity of central AMPA receptors and enhance synaptic excitation in vivo.

Action Potentials↗
PubMed2001

Thiazolidinediones and glucocorticoids synergistically induce differentiation of human adipose tissue stromal cells: biochemical, cellular, and molecular analysis.

While adipocyte differentiation has been studied extensively in murine cultures, the lack of a readily available preadipocyte model has hindered equivalent studies in man. We describe methods for the isolation and culture of primary human stromal cells from surgical adipose tissue specimens. In vitro, the stromal cells rapidly differentiate in response to a combination of adipogenic agents. Among these, glucocorticoids and thiazolidinediones act together to induce the formation of lipid vacuoles within the cells. These morphologic changes accompany the increased expression of 2 characteristic adipocyte proteins, the cytoplasmic enzyme glycerol phosphate dehydrogenase (GPDH) and the secreted cytokine leptin. Likewise, stromal cell differentiation results in elevated mRNA levels for the fatty acid binding protein aP2 and the adipogenic regulatory transcription factors CCAAT/enhancer binding protein alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma (PPARgamma) in addition to leptin. The in vitro differentiated stromal cells exhibit a lipolytic response to beta-adrenergic agonists, comparable to that reported with primary human adipocytes. These studies demonstrate the validity of human adipose tissue-derived stromal cells as a reliable in vitro model for investigations of adipocyte metabolism in humans.

Adipose Tissue↗
PubMed2000

LY377770, a novel iGlu5 kainate receptor antagonist with neuroprotective effects in global and focal cerebral ischaemia.

We have evaluated the neuroprotective effects of the decahydroisoquinoline LY377770, a novel iGlu5 kainate receptor antagonist, in two models of cerebral ischaemia. Global ischaemia, induced in gerbils by bilateral carotid artery occlusion (BCAO) for 5 min, produced a large increase in locomotor activity at 96 hr post-occlusion and a severe loss of CA1 cells in the hippocampus histologically at 120 hr post-occlusion. LY377770 (80 mg/kg i.p. 30 min before or 30 min after BCAO followed by 40 mg/kg i.p. administered at 3 and 6 hr after the initial dose) attenuated the ischaemia-induced hyperactivity and provided (92%) and (29%) protection in the CA1 cells respectively. This protection was greater than that seen with maximally tolerated doses of other glutamate receptor antagonists (CGS19755, CPP, MK-801, ifenprodil, eliprodil, HA-966, ACEA1021, L701,324, NBQX, LY293558, GYKI52466 and LY300164). Focal ischaemia was induced by infusing 200 pmol of endothelin-1 (Et-1) adjacent to the middle cerebral artery and LY377770 was administered at 80 mg/kg i.p. immediately, 1 or 2 hr post-occlusion followed by 40 mg/kg i.p. 3 and 6 hr after the first dose. The infarct volume, measured 72 hr later, was reduced by LY377770 when given immediately (P<0.01), at 1 hr (P<0.05) but not significantly at 2 hr post-occlusion. Reference compounds, LY293558 (20 mg/kg i.p. and then 10 mg/kg as above) and MK-801 (2.5 mg/kg i.p. ), both administered immediately post-occlusion produced significant (P<0.05) but somewhat less neuroprotection. In parallel microdialysis studies, LY377770 (75 mg/kg i.p.) attenuated ischaemia-induced increases in extracellular levels of glutamate, but not of dopamine. In conclusion, these results indicated that iGlu5 kainate receptors play a central role in ischaemic brain damage following global and focal cerebral ischaemia. LY377770 is a novel, soluble, systemically active iGlu5 antagonist with efficacy in global and focal ischaemia, even when administered post-occlusion. LY377770 may therefore be useful as a neuroprotectant in man.

Animals↗
PubMed2000

Deliberate self-harm in adolescents in Oxford, 1985-1995.

Deliberate self-harm (DSH) has been one of the major health problems of adolescents in the U.K. for many years. Any changes in rates of DSH or the demographic characteristics of the patient population are likely to have important implications for clinical services and for future suicidal behaviour. Following a decline in rates in the late 1970s and mid 1980s, there were signs in the late 1980s that rates were beginning to increase again. We have used data collected by the Oxford Monitoring System for Attempted Suicide on the basis of patients presenting to the general hospital in Oxford to review trends in DSH in under 20-year-olds between 1985 and 1995. There was a substantial increase in the numbers of teenage DSH patients during the 11-year study period, with an increase between 1985-1986 and 1994-1995 of 27.7% in males, 28.3% in females, and 28.1% overall. There were no demographic changes within the catchment area to explain a change of this size. As rates of repetition of DSH also increased in both sexes during the study period the overall number of episodes of DSH rose even more between 1985-1986 and 1994-1995 (+56.9% in males, +46.3% in females, and +49.4% overall). As in previous studies the majority of adolescents had interpersonal problems and/or difficulties with studying or employment. Self-poisoning with paracetamol and paracetamol compounds became increasingly common such that by 1995 these were used in almost two-thirds of overdoses. The recent increase in DSH in adolescents has important implications for general hospital and adolescent psychiatric services. The greater frequency of repetition of DSH may herald increased future suicide rates. The case for restricting the amount of paracetamol available is overwhelming. Evaluative trials of specific interventions following adolescent DSH are urgently required.

Adolescent↗
PubMed2000

Neuroprotective effects of LY379268, a selective mGlu2/3 receptor agonist: investigations into possible mechanism of action in vivo.

The mechanisms underlying the neuroprotective effects of the group II metabotropic glutamate receptor (mGluR) agonist LY379268 were investigated in a gerbil model of global ischemia. LY379268 (10 mg/kg i.p.) 30 or 60 min after 5-min bilateral carotid artery occlusion (BCAO) attenuated the ischemia-induced hyperactivity and provided protection in the CA1 hippocampal cells. This neuroprotective effect was maintained (P <.001) when histological analysis was performed 14 and 28 days after BCAO. Furthermore, 24- or 48-h pretreatment with LY379268, 10 mg/kg i.p., before 5-min BCAO markedly reduced (P <.001 and P <.05, respectively) the damage to CA1 hippocampal neurons. This result is consistent with the induction of neuroprotective factors or a very long brain half-life. To study the possible induction of neuroprotective factors as contributing to this action of LY379268, brains were examined for expression of neurotrophic factors. Results indicated that LY379268 (10 mg/kg i.p.) failed to alter the expression of transforming growth factor-beta, brain-derived neurotrophic factor, nerve growth factor, and basic fibroblast growth factor in the hippocampal regions of brains taken from gerbils sacrificed at 6, 24, 72, and 120 h postinjection. The new group II mGlu antagonist, LY341495, administered 1 h before 5-min BCAO, attenuated the neuroprotective effect of LY379268 administered 24 h before 5-min BCAO. Complementary pharmacokinetic studies showed that a significant receptor-active concentration persisted in the brain 24 h after LY379268 10 mg/kg i.p. We conclude that group II mGluR occupancy, rather than induction of neuroprotective factors, explains the long-lasting neuroprotective effect of LY379268 in the gerbil model of global ischemia.

Amino Acids↗
PubMed1999

LY379268, a potent and selective Group II metabotropic glutamate receptor agonist, is neuroprotective in gerbil global, but not focal, cerebral ischaemia.

The neuroprotective effects of a selective Group II metabotropic glutamate receptor (mGluR) agonist, LY379268, have been evaluated against global and focal cerebral ischaemia. Loss of CA1 hippocampal neurones following 5 min bilateral occlusion of the carotid artery (BCAO) in the gerbil was almost completely prevented by LY379268 (10 mg/kg, i.p.) given 30 min post-occlusion (P < 0.001); 10 mg/kg 1 h after and 20 mg/kg 2 h after BCAO also produced significant neuroprotection (P < 0.05). Similarly the BCAO-induced increase in TUNEL positive cells at 5 days post-occlusion was reduced by LY379268. By contrast the size of the infarct following middle cerebral artery occlusion (MCAO) induced by endothelin-1 infusion in the rat was unaffected by either 10 or 20 mg/kg i.p. of LY379268. This contrast between the results from these two animal models with LY379268, agrees with previous data on a less potent but similarly selective mGluR2/3 agonist, LY354740. It further suggests that mGluR Group II agonists are likely to have more utility in global, than in focal, cerebral ischaemia.

Amino Acids↗