PubMed Health⌕ Search

Biomedical subjects

L Duggan

Publications and source records attributed to L Duggan.

At least 19 recordsLinked to original sources
PubMed2005

Olanzapine for schizophrenia.

BACKGROUND: Olanzapine is an atypical antipsychotic reported to be effective without producing disabling extrapyramidal adverse effects associated with older, typical antipsychotic drugs. OBJECTIVES: To determine the clinical effects and safety of olanzapine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses. SEARCH STRATEGY: We updated the first search [Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974-1999) and The Cochrane Schizophrenia Group's Register (October 2000)] in October 2004 using the Cochrane Schizophrenia's Group's register of trials. We also searched references of all included studies for further trials, and contacted relevant pharmaceutical companies and authors. SELECTION CRITERIA: We included all randomised clinical trials comparing olanzapine with placebo or any antipsychotic treatment for people with schizophrenia or schizophreniform psychoses. DATA COLLECTION AND ANALYSIS: We independently extracted data and, for homogeneous dichotomous data, calculated the random effects relative risk (RR), the 95% confidence intervals (CI) and the number needed to treat (NNT) on an intention-to-treat basis. For continuous data we calculated weighted mean differences. MAIN RESULTS: Fifty five trials are included (total n>10000 people with schizophrenia). Attrition from olanzapine versus placebo studies was >50% by six weeks, leaving interpretation of results problematic. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (any dose, 2 RCTs n=418, RR 0.88 CI 0.8 to 0.1, NNT 8 CI 5 to 27). Although dizziness and dry mouth were reported more frequently in the olanzapine-treated group, this did not reach statistical significance. The olanzapine group gained more weight. When compared with typical antipsychotic drugs, data from several small trials are incomplete. With high attrition in both groups (14 RCTs, n=3344, 38% attrition by six weeks, RR 0.81 CI 0.65 to 1.02) the assumptions included in all data are considerable. For the short term outcome of 'no important clinical response', olanzapine seems as effective as typical antipsychotics (4 RCTs, n=2778, RR 0.90 CI 0.76 to 1.06). People allocated olanzapine experienced fewer extrapyramidal adverse effects than those given typical antipsychotics. Weight change data for the short term are not statistically significant but results between three to 12 months suggest a clinically important average gain of four kilograms for people given olanzapine (4 RCTs, n=186, WMD 4.62, CI 0.6 to 8.64). Twenty three percent of people in trials of olanzapine and other atypical drugs left by eight weeks; 48% by three to12 months (11 RCTs, n=1847, RR 0.91 CI 0.82 to 1.00). There is little to choose between the atypicals, although olanzapine may cause fewer extrapyramidal adverse effects than other drugs in this category. Olanzapine produces more weight gain than other atypicals with some differences reaching conventional levels of statistical significance (1 RCT, n=980, RR gain at 2 years 1.73 CI 1.49 to 2.00, NNH 5 CI 4 to 7). There are very few data for people with first episode illness (1 RCT, duration 6 weeks, n=42). For people with treatment-resistant illness there were no clear differences between olanzapine and clozapine (4 RCTs, n=457). AUTHORS' CONCLUSIONS: The large proportion of participants leaving studies early in these trials makes it difficult to draw firm conclusions on olanzapine's clinical effects. For people with schizophrenia it may offer antipsychotic efficacy with fewer extrapyramidal adverse effects than typical drugs, but more weight gain. There is a need for further large, long-term randomised trials with more comprehensive data.

Antipsychotic Agents↗
PubMed2004

Antipsychotic medication versus placebo for people with both schizophrenia and learning disability.

BACKGROUND: Antipsychotic medication is the standard treatment for people with learning disability and schizophrenia. OBJECTIVES: To determine the effects of any antipsychotic medication compared with placebo for treating people with a dual diagnosis of learning disability and schizophrenia. SEARCH STRATEGY: For this update we searched the Cochrane Schizophrenia Group's Register of trials (July 2004), relevant reference lists and sought unpublished data from pharmaceutical companies. SELECTION CRITERIA: We included all randomised clinical trials of longer than one month's duration, involving people with both schizophrenia and learning disability (a measured IQ of 70 or less) that evaluated antipsychotic medication versus placebo. DATA COLLECTION AND ANALYSIS: We reliably selected and assessed studies for methodological quality. Two reviewers, working independently, extracted data. We would have analysed dichotomous data on an intention-to-treat basis and presented continuous data with 65% completion rate. For dichotomous outcomes, our intention was to estimate a fixed effect relative risk (RR) with the 95% confidence interval (CI) together with the number needed to treat/harm (NNT/H). MAIN RESULTS: We found only one relevant randomised trial using our search method and this had to be excluded. This study included four people with a dual diagnosis of schizophrenia and learning disability, but results were only available for two of the participants. It was unclear as to which groups the other two people were allocated. In order to display the data, we would have had to have made too many assumptions about these two people and any results would be uninformative and potentially misleading. REVIEWERS' CONCLUSIONS: Using the methods described we found no randomised controlled trial evidence to guide the use of antipsychotic medication for people with both learning disability and schizophrenia. Until the urgent need for randomised controlled trials is met, clinical practice will continue to be guided by extrapolation of evidence from randomised controlled trials involving people with schizophrenia, but without learning disability, and non-randomised trials of those with learning disability and schizophrenia.

Adult↗
PubMed2004

Antipsychotic medication for challenging behaviour in people with learning disability.

BACKGROUND: The term 'challenging behaviour', in the absence of psychiatric disorder, encompasses a wide range of behaviours that may be harmful to people or property, may be difficult to manage and may limit access to community facilities. Antipsychotic medications have been used to modify such behaviours in people with learning disability, but there is little evidence to suggest that the benefits outweigh the risks. OBJECTIVES: To determine the effectiveness of antipsychotic medication for people with learning disability and challenging behaviour without additional mental illness. SEARCH STRATEGY: Biological Abstracts, the Cochrane Library, EMBASE, MEDLINE, PsycINFO and BIOSIS were searched. Further references were sought from published trials and pharmaceutical companies. Trials were reliably identified and data extracted. SELECTION CRITERIA: All randomised controlled trials of antipsychotic medication versus placebo. DATA COLLECTION AND ANALYSIS: Reviewers independently evaluated and analysed data on an intention to treat basis. Data were evaluated at 4, 8 and 12 weeks as longer follow-up data were not available. Reviewers assumed that those subjects lost to follow-up had a bad outcome. MAIN RESULTS: Only nine randomised controlled trials could be included in the analyses. These provided no evidence of whether antipsychotic medication helps or harms adults with learning disability and challenging behaviour. REVIEWERS' CONCLUSIONS: There are limited data on this important issue and more research is urgently needed.

Adult↗
PubMed2004

Assessing the needs of people with learning disabilities and mental illness: development of the Learning Disability version of the Cardinal Needs Schedule.

BACKGROUND: People with learning disability (LD) experience a range of mental health problems. They are a complex population, whose needs are not well understood. This study focuses on the development of a systematic process of needs assessment for this population. METHODS: The Cardinal Needs Schedule used in general psychiatry was adapted for people with learning disabilities (LD). The Learning Disability version of the Cardinal Needs Schedule (LDCNS) was tested on a sample of 35 people with LD and mental illness for its inter-rater reliability. RESULTS: The inter-rater reliability (Kappa) was calculated for 22 areas of functioning assessed by the LDCNS. Overall, there was very good agreement in seven areas, moderate agreement in six areas, fair agreement in three areas and poor agreement in one area. In four areas of functioning, Kappa could not be calculated. More needs were found in the social domain than in the clinical domain. CONCLUSION: A systematic needs assessment schedule (LDCNS) was developed for people with LD and mental illness. The inter-rater reliability is generally acceptable, but requires further examination.

Adult↗
PubMed2004

Towards in vivo TLD dosimetry in mammography.

While phantoms are used for quality control assessment of the mammography unit, in vivo dose measurements are necessary to account for the variation in size and composition of the female breast. The use of thermoluminescent dosimeters (TLDs) in mammography has been limited due to TLD visibility. The aim of this current investigation was to access the suitability of a paper-thin LiF:Mg,Cu,P TLD (GR-200F) for in vivo dosimetric mammography measurements. The visibility of GR-200F has been directly compared with LiF:Mg,Cu,P TLDs (GR-200A) using a number of commercially available phantoms. The phantoms of thickness 2-5 cm were imaged over the range of tube potentials (24-28 kVp) used clinically. Both types of TLD were placed on the surface of the phantoms allowing assessment of visibility, entrance surface dose (ESD) and field homogeneity. In vivo assessment of ESD and visibility was also carried out on a volunteer undergoing a routine mammography examination. The positions of the GR-200F TLDs were not identified either on the image of the Leeds TOR(MAM) phantom or the patient mammograms. The average ESD for the Leeds phantom was 8.8 mGy, while the patient ESD was 13 mGy. It is now possible to perform in vivo measurements with the potential of increasing the accuracy of the doses measured for women that do not conform to a standard breast thickness or density.

Breast Neoplasms↗
PubMed2003

Investigation of dose reduction in neonatal radiography using specially designed phantoms and LiF:Mg,Cu,P TLDs.

Many departments still do not use recommended radiographic parameters to X-ray neonates. Direct, accurate dose measurements of individual examinations may assist a department in justifying technique modifications that provide a substantial dose reduction without a significant loss of image quality. The aim of this study was to investigate dose reduction techniques for neonates in the intensive care unit. Alterations in beam energy (kVp and filtration) and collimation were investigated using specially designed phantoms mimicking a 700 g and 2000 g neonate, and ultrasensitive LiF:Mg,Cu,P thermoluminescence dosimeters (TLDs). Differences in entrance surface dose (ESD) and dose at depth (3 cm or 5 cm) were compared for two, overlapping fields centred individually on the chest and abdomen (Technique 1) and one large chest-abdomen field (Technique 2 or babygram). The large phantom was irradiated at 54 kVp, 60 kVp and 70 kVp without additional filtration and at 66 kVp and 70 kVp with a rare-earth hafnium filter. Focus-film distance (FFD) and mAs were adjusted to maintain optical density (OD) on each radiograph. The baseline dose at 54 kVp and 100 cm FFD was (46+/-2) micro Gy. Increasing the tube potential from 54 kVp to 70 kVp without additional filtration reduced the ESD by 27%. However, the addition of a 0.05 mm hafnium filter at 66 kVp further reduced the radiation dose by 13%, to produce an ESD of (28+/-2) micro Gy. All contrast details were observable at 66 kVp with hafnium filtration. Technique 1 may lead to an increase in effective dose due to field overlap, which diverges at depth, and increased scatter at the periphery of the fields.

Critical Care↗
PubMed2002

Interventions for learning disabled sex offenders.

BACKGROUND: The management of sex offenders is a major public concern. Behavioural and pharmacological interventions have been used for many years and more recently cognitive behavioural based interventions have become popular around the world. Programmes designed for the general population have been modified for those sex offenders with learning disability, to address their cognitive deficits. The efficacy of these modified programmes is unclear. OBJECTIVES: To determine the efficacy of interventions with learning disabled sex offenders. SEARCH STRATEGY: The reviewers searched electronically EMBASE, PsycINFO, Medline, Cinahl, Cochrane Library, SPECTR, National Clearinghouse on Child Abuse and Neglect Information and National Criminal Justice Reference Service and Biological Abstracts. SELECTION CRITERIA: All randomised controlled trials comparing an intervention for learning disabled sex offenders to any other, or no intervention. DATA COLLECTION AND ANALYSIS: Data were independently extracted. MAIN RESULTS: No randomised controlled trial was identified. REVIEWER'S CONCLUSIONS: Using the methods described the reviewers found no randomised controlled trial evidence to guide the use of interventions for learning disabled sex offenders. Until the urgent need for randomised controlled trials is met, clinical practice will continue to be guided by either extrapolation of evidence from randomised controlled trials involving sex offenders without learning disability or non-randomised trial evidence of interventions for the learning disabled sex offender.

Androgen Antagonists↗
PubMed2002

LiF:Mg,Cu,P 'pin worms': miniature detectors for brachytherapy dosimetry.

Dose measurements in brachytherapy 192Ir implants are often difficult due to large dose gradients and complex photon spectra. Therefore, tissue-equivalent detectors with a high spatial resolution, such as the highly promising LiF:Mg,Cu,P thermoluminescent detectors (TLDs) are required. It was the aim of the present work to ascertain if miniature LiF:Mg,Cu,P TLDs can effectively measure the dose distribution around 192Ir implants. 'Pin worm' TLDs (type MCP, diameter 0.6 mm, length 2 mm) were compared with GR-200R (SSDL, Beijing) rods cut in half. The TLDs were tested for reproducibility and energy dependence using high dose rate (HDR) and low dose rate (LDR) brachytherapy units. 192Ir measurements were performed in a tissue equivalent phantom accommodating hollow needles and catheters routinely used in brachytherapy. Pin worms had an average reproducibility of less than +/-2% (1 SD) and a detection limit of less than 10 microGy. The small dimensions of the pin worms allowed their placement within brachytherapy needles and catheters. The measured relative dose distribution was in good agreement with the predictions of a computerised treatment planning system (ADAC Pinnacle); however, limitations in the TLD energy correction did not allow for absolute dose comparison.

Brachytherapy↗
PubMed2001

Snf1--a histone kinase that works in concert with the histone acetyltransferase Gcn5 to regulate transcription.

Modification of histones is an important element in the regulation of gene expression. Previous work suggested a link between acetylation and phosphorylation, but questioned its mechanistic basis. We have purified a histone H3 serine-10 kinase complex from Saccharomyces cerevisiae and have identified its catalytic subunit as Snf1. The Snf1/AMPK family of kinases function in conserved signal transduction pathways. Our results show that Snf1 and the acetyltransferase Gcn5 function in an obligate sequence to enhance INO1 transcription by modifying histone H3 serine-10 and lysine-14. Thus, phosphorylation and acetylation are targeted to the same histone by promoter-specific regulation by a kinase/acetyltransferase pair, supporting models of gene regulation wherein transcription is controlled by coordinated patterns of histone modification.

Acetylation↗
PubMed2001

Purification and characterization of human cell--cell adhesion molecule 1 (C-CAM1) expressed in insect cells.

The cell--cell adhesion molecule 1 (C-CAM1) plays an important role as a tumor suppressor for prostate cancer. Decreased expression of C-CAM1 was detected in prostate, breast, and colon carcinoma. Reexpression of C-CAM1 in prostate and breast cancer cell lines was able to suppress tumorigenicity in vivo. These observations suggest that C-CAM1 may be used as a marker for cancer detection or diagnosis. To generate monoclonal antibodies specific to C-CAM1, we have overexpressed full-length human C-CAM1 in Sf9 cells using a baculovirus expression system. The protein was purified 104-fold using nickel affinity chromatography. About 0.4 mg purified C-CAM1 was obtained from 200 mg of infected cells. When the purified protein was digested with peptidyl-N-glycosidase, the apparent mobility of the protein on SDS--PAGE changed from 90 to 58 kDa, which is close to the molecular weight predicted from the cloned cDNA sequence. This observation suggests that C-CAM1 was glycosylated on asparagine residues when expressed in Sf9 cells. Western blotting and internal protein sequencing analysis confirmed that the purified protein is human C-CAM1. Biochemical and functional assays indicate that this protein expressed in Sf9 cells displays characteristics similar to those of native protein, including adhesion function and glycosylation modification. Using this protocol, sufficient quantity of this protein can be produced with purity suitable for monoclonal antibody generation and biochemical study.

Adenosine Triphosphatases↗
PubMed2000

Antipsychotic medication for those with both schizophrenia and learning disability.

BACKGROUND: Antipsychotic medication is the standard treatment for people with learning disability and schizophrenia. OBJECTIVES: To determine the efficacy of any antipsychotic medication for treating people with a dual diagnosis of learning disability and schizophrenia. SEARCH STRATEGY: Electronic searching of Biological Abstracts, the Cochrane Schizophrenia Group's Register of trials, the Cochrane Library, EMBASE, PsycLIT and MEDLINE. Unpublished data were sought from pharmaceutical companies. Both authors independently selected the relevant studies from the reports identified in this way. SELECTION CRITERIA: 1. All randomised controlled trials of antipsychotic medication, regardless of dosage, versus a placebo control, of longer than one month's duration. 2. Anyone over 18 years of age with both learning disability and schizophrenia. Learning disability was defined as a measured IQ of 70 or less. Any mode of diagnosis of schizophrenia was acceptable. DATA COLLECTION AND ANALYSIS: The two reviewers independently attempted to select and then extract data but it was not possible to do this with the single study that met the inclusion criteria. MAIN RESULTS: Only one relevant randomised trial was found by the searches. This study included four people with a dual diagnosis of schizophrenia and learning disability, but results were available for only two. The groups to which the other two people were allocated were unclear. In order to display the data, too many assumptions would have to have been made about these other two people and any results would be uninformative and potentially misleading. REVIEWER'S CONCLUSIONS: Using the methods described the reviewers found no randomised controlled trial evidence to guide the use of antipsychotic medication for those with both learning disability and schizophrenia. Until the urgent need for randomised controlled trials is met clinical practice will continue to be guided by extrapolation of evidence from randomised controlled trials involving people with schizophrenia but without learning disability and non-randomised trials of those with learning disability and schizophrenia.

Antipsychotic Agents↗
PubMed2000

Antipsychotic medication for challenging behaviour in people with learning disability.

BACKGROUND: The term 'challenging behaviour', in the absence of psychiatric disorder, encompasses a wide range of behaviours that may be harmful to people or property, may be difficult to manage and may limit access to community facilities. Antipsychotic medications have been used to modify such behaviours in people with learning disability, but there is little evidence to suggest that the benefits outweigh the risks. OBJECTIVES: To determine the effectiveness of antipsychotic medication for people with learning disability and challenging behaviour. SEARCH STRATEGY: Biological abstracts, the Cochrane Library, the Cochrane Schizophrenia Group's Register, EMBASE, MEDLINE, PsycLIT were searched. Further references were sought from published trials and pharmaceutical companies. Trials were reliably identified and data extracted. SELECTION CRITERIA: All randomised controlled trials of antipsychotic medication versus placebo. DATA COLLECTION AND ANALYSIS: Reviewers independently evaluated and analysed data on an intention to treat basis. Data were evaluated at 4 and 8 weeks as longer follow-up data were not available. Reviewers assumed that those subjects lost to follow-up had a bad outcome. MAIN RESULTS: Only three randomised controlled trials could be included in the analyses. These provided no evidence of whether antipsychotic medication helps or harms adults with learning disability and challenging behaviour. REVIEWER'S CONCLUSIONS: There is limited data on this important issue and more research is urgently needed.

Adult↗
PubMed2000

Olanzapine for schizophrenia.

BACKGROUND: Olanzapine is an atypical antipsychotic that is reported to be effective without producing the disabling extrapyramidal side effects associated with the older, typical antipsychotic drugs. OBJECTIVES: To determine the clinical effects and safety of olanzapine as compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses. SEARCH STRATEGY: The reviewers undertook electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), The Cochrane Schizophrenia Group's Register (September 1999), EMBASE (1980-1999), MEDLINE (1966-1999), and PsycLIT (1974-1999). References of all identified studies were searched for further trials, and the reviewers contacted relevant pharmaceutical companies and authors of trials. SELECTION CRITERIA: All randomised clinical trials comparing olanzapine to placebo or any antipsychotic treatment for those with schizophrenia or schizophreniform psychoses. DATA COLLECTION AND ANALYSIS: Data were independently extracted. For homogeneous dichotomous data the random effects relative risk (RR), the 95% confidence intervals (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data the reviewers calculated weighted mean differences. MAIN RESULTS: Twenty trials are included. Attrition from olanzapine versus placebo studies was so great (olanzapine - 61%, placebo - 73% by six weeks, RR 0.85 CI 0. 7-0.98, NNT 8 CI 5-40) that interpretation of results is problematic. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (RR 0.88 CI 0.8-0.98, NNT 8 CI 5-27), but trial data regarding negative symptoms are equivocal for this comparison. Dizziness and dry mouth were more common in the olanzapine-treated group, and, although not statistically significant, the olanzapine group gained more weight. Data from several small trials are incomplete; but, for the short term outcome of 'no important clinical response', olanzapine seem as effective as typical antipsychotics (n=2778, RR 0.9 CI 0.76-1.06). Brief Psychiatric Rating Scale (BPRS) data tended to be equivocal but Positive and Negative Syndrome Scale (PANSS) rating of total score and negative and positive symptom sub-scores favoured olanzapine. With high attrition in both groups (olanzapine - 36%, typical drug - 49% by 6 weeks, n=2738, RR 0.85 CI 0.66-1.1; olanzapine - 83%, typical drug - 90% by 1 year, n=2738, RR 0.9 CI 0. 86-1.02), the assumptions included in all continuous data are considerable. Participants allocated olanzapine experienced fewer extrapyramidal side effects than people given haloperidol. Weight change data for the short term are not conclusive (n=2455, WMD 0.8kg CI -0.6-2.2) but the three to 12 month results suggest an average gain of four kilograms (n=233, WMD 4 CI 0.3-7.8). It is difficult to distinguish between olanzapine and other atypical drugs, although it may cause fewer extrapyramidal side effects than risperidone (n=339, RR 0.6 CI 0.4-0.9, NNH 8 CI 4-29). Olanzapine did cause more weight gain than its comparators but current data are not statistically significant (3-12 months, n=535, WMD 2.2kg CI -0.6-5). One study (n=180) found no clear differences between olanzapine and clozapine for people with treatment-resistant illness. REVIEWER'S CONCLUSIONS: For people with schizophrenia olanzapine may offer antipsychotic efficacy with fewer extrapyramidal side effects than typical drugs but more weight gain. The large proportions of participants leaving the studies early, in the large multi-centre trials makes it difficult to draw firm conclusions on clinical effects. Large, long-term randomised trials with participants, interventions and primary outcomes that are familiar to those wishing to help those with schizophrenia are long overdue.

Antipsychotic Agents↗
PubMed2000

Risperidone versus other atypical antipsychotic medication for schizophrenia.

BACKGROUND: Risperidone is one of a number of 'atypical antipsychotics' which are currently being marketed for the treatment of those with schizophrenia, largely on the basis of claims of improved tolerability and effectiveness compared to much cheaper conventional antipsychotics. The efficacy of risperidone has already been compared to conventional drugs, but it remains unclear how risperidone compares with other atypical antipsychotic drugs such as clozapine. OBJECTIVES: To determine the effects of risperidone compared with other atypical antipsychotic drugs for schizophrenia. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 2000), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1999), PSYNDEX (1977-1999) and PsycLIT (1974-1999) were undertaken. In addition, pharmaceutical databases on the Dialog Corporation Datastar and Dialog services were searched. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted. SELECTION CRITERIA: All randomised controlled clinical trials that compared risperidone to other atypical antipsychotic treatments for schizophrenia and schizophrenia-like psychoses were included by independent assessment. DATA COLLECTION AND ANALYSIS: Citations and, where possible, abstracts were independently inspected by reviewers, papers ordered, re-inspected and quality assessed. Data were independently extracted. For homogeneous dichotomous data the risk ratio (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) were calculated on an intention-to-treat basis. For continuous data, standardised and weighted mean differences were calculated (SMD, WMD). All data were inspected for heterogeneity. MAIN RESULTS: Nine studies were obtained, comparing risperidone with clozapine (five studies - largely amongst treatment resistant patients); olanzapine (three studies); and amisulpiride (one study). The research was beset by problems of high attrition rates and short term follow up. Clozapine does seem equally acceptable to risperidone in the short term (leaving the study early, n=466, RR 1. 00 CI 0.73-1.37). For most other outcomes wide confidence intervals were obtained, which meant that it was impossible to judge whether the two compounds were equally effective, or whether one was in fact superior to the other. Olanzapine and risperidone seem broadly similar according to numbers of patients responding to treatment (40% reduction in PANSS scores: n=339, RR 1.14, CI 0.99-1.32). Olanzapine caused fewer people to leave the study early (n=404, RR 1. 31 CI 1.06-1.60; NNT 8 CI 4-32) and fewer extrapyramidal side effects (n=339, RR 1.67 CI 1.14-2.46; NNH 8 CI 5-33), although comparative doses of risperidone were higher than those recommended in practice. In one single study (n=228) amisulpiride seemed broadly similar to risperidone in most respects. There were no useful data presented relating to service use and costs. Very few data relating to quality of life were presented. REVIEWER'S CONCLUSIONS: The equivalence of clozapine and risperidone for treatment resistant schizophrenia cannot yet be assumed and there seems to be little to chose between risperidone and both olanzapine and amisulpiride. The research is limited in many respects, and longer term studies measuring clinically important outcomes, including service use and quality of life are needed to judge the comparative value of the various atypical drugs.

Antipsychotic Agents↗
PubMed2000

Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14.

Multiple covalent modifications exist in the amino-terminal tails of core histones, but whether a relationship exists between them is unknown. We examined the relationship between serine 10 phosphorylation and lysine 14 acetylation in histone H3 and have found that, in vitro, several HAT enzymes displayed increased activity on H3 peptides bearing phospho-Ser-10. This augmenting effect of Ser-10 phosphorylation on acetylation by yGcn5 was lost by substitution of alanine for arginine 164 [Gcn5(R164A)], a residue close to Ser-10 in the structure of the ternary tGcn5/CoA/histone H3 complex. Gcn5(R164A) had reduced activity in vivo at a subset of Gcn5-dependent promoters, and, strikingly, transcription of this same subset of genes was also impaired by substitution of serine 10 to alanine in the histone H3 tail. These observations suggest that transcriptional regulation occurs by multiple mechanistically linked covalent modifications of histones.

Acetylation↗
PubMed2000

Verification of the dose distribution for 192Ir mould treatments using radiochromic film and LiF:Mg,Cu,P TLDs.

Radioactive moulds are an effective way of treating skin lesions. The aim of the study was to verify the dose distribution in a low dose rate 192Ir hand mould treatment using radiochromic film and LiF:Mg,Cu,P TLDs. Measurements were compared with two computerised treatment planning systems--Theraplan VO5B and ADAC Pinnacle3 V4.0b. Radiochromic film measured doses that were typically 25-30% lower than the TLD and planning computer doses (which agreed within +/- 5%). However, radiochromic film provided a two-dimensional map, which is particularly useful for dose distributions that are difficult to predict. This was demonstrated in the effects of adding thumb shielding to the hand mould. TLD results provided only point dose verification. Dose rates to the inner surface of the thumb were reduced from 15-20 cGy/hr to 2-4 cGy/hr by using 7.5 mm lead shielding. This is consistent with three half value layer reductions. For unshielded treatments, TLD results agreed with the treatment planning computers all within +/- 13%, including an uncertainty of +/- 10% on the source strength certificate for the activity. Due to the detector's sensitivity, miniaturisation would be the next approach for further more accurate verification with LiF:Mg,Cu,P TLDs.

Brachytherapy↗