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Biomedical subjects

M Fenton

Publications and source records attributed to M Fenton.

At least 37 records · Page 2Linked to original sources

Individual psychodynamic psychotherapy and psychoanalysis for schizophrenia and severe mental illness.

BACKGROUND: People with schizophrenia and severe mental illness may need much support from health care professionals, in most cases over a long period of time. Research on the effects of psychotherapy for schizophrenia shows mixed results. Although pharmacological interventions remain the treatment of choice for schizophrenia patients, it is also of interest to look at the effects of treatment methods focusing on psychosocial factors affecting schizophrenia. OBJECTIVES: To review the effects of individual psychodynamic psychotherapy and/or psychoanalysis for people with schizophrenia or severe mental illness. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1985-1999), CINAHL (1982-1999), The Cochrane Library CENTRAL (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (1999), Dissertation Abstracts On disc (1866-1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974-1999), and Sociofile (1974-1998) were made. Authors of included trials were contacted for information on further trials. SELECTION CRITERIA: All randomised trials of individual psychodynamic psychotherapy or psychoanalysis for people with schizophrenia or severe mental illness (however defined) were selected. DATA COLLECTION AND ANALYSIS: Data were independently extracted by at least two reviewers. For dichotomous data relative risks (RR) were calculated and for continuous data weighted mean differences (WMD) between groups were calculated. MAIN RESULTS: No trials of a psychoanalytic approach were identified. Data are sparse for all comparisons involving a psychodynamic approach. There is no evidence of any positive effect of psychodynamic therapy and the possibility of adverse effects seems never to have been considered. The psychodynamic approach may be more acceptable to people than a more cognitive reality-adaptive therapy. REVIEWER'S CONCLUSIONS: Current data do not support the use of psychodynamic psychotherapy techniques for hospitalised people with schizophrenia. If psychoanalytic therapy is being used for people with schizophrenia there is an urgent need for trials.

Humans↗

Loxapine for schizophrenia.

BACKGROUND: Loxapine is a drug with D2/D3 receptor antagonist activity and a higher affinity for D3 than D2. Some authors have suggested that loxapine is more effective than typical antipsychotics in reducing the negative symptoms of schizophrenia, that extrapyramidal side-effects are not usually seen at clinically effective antipsychotic doses and that it should therefore be classed as atypical. OBJECTIVES: To determine the effects of loxapine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1996), PSYNDEX (1977-1995) 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 relevant to the care of schizophrenia that compared loxapine to other treatments. 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 but excluded if loss to follow up was greater than 50%. 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, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity. MAIN RESULTS: Compared to placebo, loxapine is antipsychotic (Global effect - not improved at 6 weeks, n=66, RR 0.6 CI 0.4-0.9 NNT 4 CI 2-62) with similar adverse effect profile to typical drugs. Is as effective as typical drugs in the short term (4-12 weeks) (Global effect - not improved, n=411, RR 0.89 CI 0.7-1.2). Very limited heterogeneous data suggest that, given intramuscularly (IM), loxapine may be at least as sedating as IM haloperidol and thiothixene. REVIEWER'S CONCLUSIONS: Loxapine is antipsychotic but its effects are under researched. It is not clearly different from typical drugs in either its positive or adverse effects.

Antipsychotic Agents↗

Thioridazine for schizophrenia.

BACKGROUND: Thioridazine is a piperidine phenothiazine used for the treatment of people with schizophrenia. It has often been considered the drug of choice in the elderly because of reputed lower levels of extrapyramidal adverse events. It may, however, be more likely to cause cognitive adverse events, such as delirium or worsening of memory, and, on rare occasions, thioridazine has caused pigmentary retinopathy. OBJECTIVES: To examine the effects of thioridazine for those with schizophrenia, and, in particular, elderly people with schizophrenia. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1980-1999), CINAHL (1982-1999), The Cochrane Library (Issue 3, 1999), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974-1999) and Sociofile (1974-1999) were undertaken. References of all identified studies were searched for further trials. Pharmaceutical companies and authors of trials were contacted. SELECTION CRITERIA: All randomised clinical trials that compared thioridazine to other treatments for people with schizophrenia or other psychoses. 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. Data were excluded if loss to follow up was greater than 40%. For homogeneous dichotomous data the Relative Risk (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, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity. MAIN RESULTS: 560 people from 11 studies were randomised to thioridazine or placebo. For change in global state, small, short term studies (three months or less) found no difference between groups (RR 0.66 CI 0.35-1.23, n=100). At six months, however, two small studies (n=65) favoured thioridazine (RR 0.34 CI 0.21-0. 56, NNT 2 CI 1-6). Fourteen percent in the thioridazine group left early compared to 32% of people allocated to placebo (RR 0.43 CI 0. 31-0.61, NNT 6 CI 4-10, n=510). Few differences in terms of adverse effects, between thioridazine and placebo, were apparent. Limited data from trials suggest that thioridazine is not strongly anticholinergic (blurred vision RR 2.01 CI 0.56-7.25, n=224). Thioridazine is not sedating (at three months to one year RR 2.48 CI 0.96-6.4, n=122). No data were presented on retinal changes. Two thousand three hundred ninety-seven patients from 26 studies were randomised to thioridazine versus typical antipsychotics. For the outcome 'no better or worse', those allocated to thioridazine were no better off than people given control typical neuroleptics (RR 0. 97 CI 0.78-1.21, n=771). There were no clear differences between thioridazine and other drugs for the outcome 'Mental state - no better or worse' on the BPRS by three months (RR 1.3 CI 0.8-2.11, n=208). Twenty-one studies (n=1737) had 19% attrition in both groups. Few differences were seen in the lists of adverse effects. As expected from the placebo comparison, thioridazine does not cause more anticholinergic-type symptoms than other drugs. About half of people given thioridazine felt drowsy or sedated but this was no different from other drugs (RR 1.06 CI 0.93-1.2, n=909). Parkinsonism was less common in the thioridazine group in the short term (RR 0.29 CI 0.12-0.7, n=340). One small study (n=40) found no clear differences between thioridazine and clozapine. REVIEWER'S CONCLUSIONS: Although there are shortcomings and gaps in the data, there appears to be enough consistency over different outcomes and periods to confirm that thioridazine is an antipsychotic of similar efficacy to other commonly used neuroleptics for people with schizophrenia. Its adverse events profile is similar to that of other drugs, but it may have a lower level of extrapyramidal problems. (ABSTRACT TRU

Aged↗

Zotepine for schizophrenia.

BACKGROUND: Typical antipsychotic drugs are widely used as first line treatment for people with schizophrenia. The atypical class of antipsychotic drugs, however, is making important inroads into this approach and zotepine is one such compound. It is a dopamine antagonist and claimed to be to be particularly effective for negative symptoms OBJECTIVES: To determine the effects of zotepine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1980-1999), CINAHL (1982-1999), The Cochrane Library (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), EMBASE (1980-1999), Dialog Corporation Datastar service (1999), MEDLINE (1966-1999), and PsycLIT (1974-1999) were undertaken. References of all identified studies were searched for further trials. Knoll Pharmaceuticals and authors of trials were contacted. SELECTION CRITERIA: All randomised clinical trials that compared zotepine to other treatments for people with schizophrenia or other psychoses were included. 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. Data were excluded if loss to follow up was greater than 50%. For homogeneous dichotomous data the relative risk (RR), 95% confidence interval (CI) and, where appropriate, the number needed to treat (NNT) and numbers needed to harm (NNH), were calculated on an intention-to-treat basis. For continuous data, weighted mean differences were calculated (WMD). All data were inspected for heterogeneity. MAIN RESULTS: All outcomes were short term (4-12 weeks). Limited data suggest that zotepine is an antipsychotic, at least as effective as typical drugs. Mental state measures of 'no clinically important improvement' favour zotepine when compared to other active drugs (n=356, RR 0.8 CI 0.7-0.9, NNT 7 CI 4-22). About one third of people in both zotepine and control groups left the studies before trial completion. Zotepine may result in less movement disorder adverse effects than typical antipsychotic drugs. Trials have not highlighted clear differences between zotepine and other atypical drugs. REVIEWER'S CONCLUSIONS: Zotepine may be a valuable addition to the increasing ranks of atypical antipsychotic drugs. More data from already existing studies is urgently needed to increase the confidence in the findings of this review. New data from well planned, conducted and reported long term pragmatic randomised trials are necessary. Otherwise clinical use of zotepine will be based on speculation on the meaning of the findings of short explanatory trials for everyday practice.

Antipsychotic Agents↗

Molindone for schizophrenia and severe mental illness.

BACKGROUND: Typical antipsychotic drugs are widely used as the first line treatment for people with schizophrenia. However, the atypical class of antipsychotic drugs is making important inroads into this approach. 'Atypical' is a term widely used to describe some antipsychotics which have a low propensity to produce movement disorders, sedation and raised serum prolactin. There is some suggestion that the different adverse effect profiles of the atypical antipsychotic group make them more acceptable to people with schizophrenia. Molindone has a similar profile to quetiapine (a novel atypical antipsychotic), with very low binding to all receptors. Some authors have suggested that molindone is safer than other 'typical' antipsychotics in that extrapyramidal adverse effects are not usually seen at clinically effective antipsychotic doses and that it should therefore be classed as an atypical antipsychotic. OBJECTIVES: To determine the effects of molindone compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1980-1999), The Cochrane Library CENTRAL (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), CINAHL (1982-1999), 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. The manufacturer of molindone and authors of trials were contacted. SELECTION CRITERIA: All randomised controlled trials that compared molindone to other 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. Data were excluded if loss to follow up was greater than 50%. 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, weighted mean differences (WMD) were calculated. All data were inspected for heterogeneity. MAIN RESULTS: Thirteen studies were included in the review. Data for this compound range from very short (10 day) studies of the intramuscular preparation to trials lasting over three months. For measures of global state available data do not justify any conclusions on the comparative efficacy of molindone and placebo. When compared to other typical antipsychotics no difference in effectiveness was evidenced (doctors' RR 1.13, CI 0.69 to 1.86; nurses' RR 1.23, CI 0.82 to 1.86). It is no more or less likely than typical drugs to cause movement disorders, but causes significantly more weight loss (RR 2.78, CI 1.10 to 6.99). REVIEWER'S CONCLUSIONS: The strength of the evidence relating to this compound is limited, owing to small sample size, poor study design, limited outcomes and incomplete reporting. Molindone may be an effective antipsychotic; however, its adverse effect profile does not differ significantly from that of typical antipsychotics, apart from the event of weight loss. At present there is no evidence to suggest that it may have an atypical profile.

Antipsychotic Agents↗

Unpublished rating scales: a major source of bias in randomised controlled trials of treatments for schizophrenia.

BACKGROUND: A recent review suggested an association between using unpublished scales in clinical trials and finding significant results. AIMS: To determine whether such an association existed in schizophrenia trials. METHOD: Three hundred trials were randomly selected from the Cochrane Schizophrenia Group's Register. All comparisons between treatment groups and control groups using rating scales were identified. The publication status of each scale was determined and claims of a significant treatment effect were recorded. RESULTS: Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison (relative risk 1.37 (95% CI 1.12-1.68)). This effect increased when a 'gold-standard' definition of treatment superiority was applied (RR 1.94 (95% CI 1.35-2.79)). In non-pharmacological trials, one-third of 'gold-standard' claims of treatment superiority would not have been made if published scales had been used. CONCLUSIONS: Unpublished scales are a source of bias in schizophrenia trials.

Humans↗

Divergent requirements for the MAPK(ERK) signal transduction pathway during initial virus infection of quiescent primary B cells and disruption of Epstein-Barr virus latency by phorbol esters.

Quiescent primary B lymphocytes and Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell lines express components of the extracellular response kinase arm of the mitogen-activated protein kinase (MAPK(ERK)) signal transduction pathway and transmit signals through the pathway when exposed to appropriate stimuli. Although the MAPK(ERK) pathway is activated following infection with EBV, MAPK/ERK kinase (MEK1) activity is not required to drive the proliferation of infected cells. However, MEK1 contributes to EBV latency control.

B-Lymphocytes↗

The efficient and rapid import of a peptide into primary B and T lymphocytes and a lymphoblastoid cell line.

Lymphocytes are notoriously difficult to transfect. The favoured technique, electroporation, has three major disadvantages: it is highly disruptive, causing large scale cell death; it is inefficient; quiescent primary lymphocytes are refractory to electroporation unless they have been partially activated. We have investigated the cellular import of the third helix of the Antennapedia homeodomain protein (pAntp) as an alternative method for introducing peptides into primary lymphocytes and lymphoid cell lines. The pAntp peptide is taken up rapidly into the cytoplasm and nucleus of the cells where it is retained for at least 48 h. The system displays none of the disadvantages of electroporation; no toxicity of the pAntp peptide was detected at the concentrations tested and the process was efficient with up to 95% of lymphocytes importing the pAntp peptide. Finally, quiescent primary lymphocytes were as efficient as activated primary lymphocytes and a lymphoid cell line at importing the pAntp peptide. This demonstrates that the pAntp peptide delivery system has major advantages over electroporation as a method of delivering molecules to lymphocytes and a lymphoid cell line.

Amino Acid Sequence↗

Interactions between Epstein-Barr virus and the cell cycle control machinery.

Epstein-Barr virus (EBV) persists in the majority of the world's human population. In the majority of cases the infection is asymptomatic, but EBV is associated with a number of human diseases, such as infectious mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, gastric carcinomas and other lymphomas and lymphoproliferative diseases. In this review the evidence linking EBV with these diseases is reviewed together with recent advances in understanding the interactions between EBV and the cell cycle control machinery.

Cell Cycle↗

Assessment of chromosome 3 copy number in ocular melanoma using fluorescence in situ hybridization.

Recent reports have indicated that monosomy 3 is a marker of poor prognosis in uveal melanoma. Fluorescence in situ hybridization (FISH) was performed on fresh touch preparations from 17 uveal, and 5 conjunctival melanomas, using the chromosome 3 centromeric probe, D3Z1. Of the 17 uveal melanomas, all of which originated in the choroid, two cases revealed a monosomy of chromosome 3. One of the conjunctival melanomas contained a major clone that was trisomic for chromosome 3, and another conjunctival melanoma contained a tetrasomic population. FISH, using the alpha-satellite probe for chromosome 3 on uveal melanoma imprints, allows one to predict which patients are potentially at a higher risk of relapse. Multiplication, rather than deletion, of copies of chromosome 3 in conjunctival melanomas may be a nonspecific aberration, perhaps indicative of polyploidy, a characteristic of tumor progression.

Adult↗

Mucin output in ileal digesta of pigs fed a protein-free diet.

Daily outputs of mucin in ileal digesta were estimated in three barrows fed a protein-free diet while administered either saline (SAI) or a complete amino acid mixture (AAI) intravenously. The water soluble-ethanol precipitable fraction of ileal digesta (crude mucin; CM) was used to estimate the composition of mucin in ileal digesta. This fraction exhibited a carbohydrate composition characteristic of mucin and had a high threonine, serine and proline content (40 mol/100 mol). The proportions of soluble gastric and intestinal mucins, approximately 27 and 73%, respectively, were estimated from the N-acetylglucosamine (GlcNAc)/N-acetylgalactosamine (GalNAc) ratio in CM. The daily outputs of soluble mucin, 2.75 and 3.41 g/day from SAI and AAI pigs (p = 0.13), respectively, were determined from the GalNAc outputs in CM, assuming the above contributions of gastric and intestinal mucins. The estimated soluble mucin outputs accounted for more than 99% of the fucose, galactose, GalNAc and GlcNAc in CM. Total mucin outputs in ileal digesta, 5.32 and 5.65 g/day from SAI and AAI Pigs (p = 0.24), respectively, were determined from the total GalNAc output in digesta, assuming soluble and insoluble mucin had similar compositions. Based on these outputs, mucin represented approximately 30, 7 to 22, 15 and 11% of the endogenous threonine, proline, serine and protein, respectively, in ileal digesta. Approximately 74, 76, 100 and 53% of the fucose, galactose GalNAc and GlcNAc, respectively, in ileal digesta from pigs in this study was attributed to mucin. The results from this study demonstrate the importance of mucin as a source of some endogenous amino acids and carbohydrates.

Acetylgalactosamine↗