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Biomedical subjects

Peter W Thomas

Publications and source records attributed to Peter W Thomas.

9 recordsLinked to original sources

Removal of lens epithelial cells and the effect on capsulorhexis size.

PURPOSE: To assess the long-term effects of lens epithelial cell (LEC) removal on capsulorhexis opening size. SETTING: Dorset County Hospital, Dorchester, United Kingdom. METHODS: This prospective randomized control study included 39 eyes of 38 patients. Twenty eyes were selected randomly for removal of LECs from the anterior capsule as part of routine cataract operation comprising phacoemulsification with intraocular lens (IOL) implantation. The other 19 eyes were used as controls in which the LECs were not removed. All surgeries were performed by 1 surgeon (A.T.). All patients had silicone IOL (Allergan SI-40) implantation. The capsulorhexis opening size was determined immediately after surgery and 2 weeks and 6 months after surgery. Data on treatment outcome of the cataract surgery were analyzed statistically. RESULTS: Six months postoperatively, the size of the capsulorhexis had statistically significant increased in the study group that had LECs removed (mean increase 1.07 +/- 1.70 mm(2); paired Student t test P=.01), whereas the capsulorhexis size had statistically significant decreased in the control group (mean decrease -3.38 +/- 2.37 mm(2); paired Student t test, P<.0001). The difference in changes in the capsulorhexis areas between the 2 groups was also highly statistically significant (independent-sample Student t test, P<.0001). CONCLUSION: Removal of anterior subcapsular LECs by aspiration helped maintain the size of the capsulorhexis opening and thus can help prevent capsule contraction syndrome.

Aged↗

A randomised trial of early warning signs relapse prevention training in the treatment of alcohol dependence.

A pragmatic randomised trial examined the effects of Early Warning Signs Relapse Prevention Training (EWSRPT) on drinking in alcohol dependent persons with history of relapse. Participants were 124 abstinent alcohol dependent patients with a history of relapse (median five relapses) who entered the trial as they completed a 6-week day treatment programme. They were randomly allocated to receive either (1) Aftercare as Usual (AU) or (2) AU plus 15 individual sessions of EWSRPT using Gorski's protocol. Assessment carried out at entry to the trial, and 4, 8, and 12 months later, included self-report of drinking, blood tests (gamma glutamyl transferase, GGT; serum alanine aminotransferase, ALT) and measures of functioning (Alcohol Problems Questionnaire, APQ; SF36, Brief Symptom Inventory, BSI; Assessment of Warning-signs of Relapse, AWARE). Intention to treat analysis found no significant differences in continuous abstinence during the follow-up year (17% of 58 AU, 31% of 58 EWSRPT, p=0.08). The EWSRPT participants had a significantly lower probability of drinking heavily (74% of AU, 55% of EWSRPT, p=0.04), and significantly fewer days drinking (p=0.05) and heavy drinking (p=0.04). These clinically worthwhile effects for a relapse-prone group justify further research into EWSRPT.

Adult↗

ZAP-70 expression and prognosis in chronic lymphocytic leukaemia.

BACKGROUND: Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease; many patients never need treatment, whereas some have poor outcomes. New treatments, which can induce complete remissions, allow patients with poor outlook to be treated while they are still asymptomatic. Whether or not the IgVH gene is mutated is the best predictor of clinical outcome, but this assay is unsuited to the routine laboratory. The gene coding for ZAP-70, a tyrosine kinase protein normally expressed in T and NK cells, has been shown by gene-expression profiling to be differentially expressed between patients with mutated and unmutated IgVH genes. We assessed whether ZAP-70 could be used as a prognostic marker in CLL. METHODS: We developed a flow cytometry assay for ZAP-70 protein expression and investigated its concordance with ZAP-70 mRNA expression, IgVH gene mutational status, and clinical outcome in 167 patients with CLL. FINDINGS: We showed high concordance between ZAP-70 protein expression and IgVH gene mutations. 108 patients (65%) had mutated IgVH genes and were ZAP-70 negative; 46 (28%) had unmutated IgVH genes and were ZAP-70 positive. Findings were discordant in 13 patients: six (4%) had mutated IgVH genes but were ZAP-70 positive, and seven (4%) had unmutated IgVH genes and were ZAP-70 negative. Expression of mRNA showed 97% concordance with ZAP-70 protein. Median survival was 24.4 years (95% CI 15.1-33.8) in ZAP-70 negative patients and 9.3 years (7.0-11.5) in those who were ZAP-70 positive (hazard ratio 5.5, 2.8-.8). INTERPRETATION: ZAP-70 protein, which can be measured by flow cytometry in the general laboratory, is a reliable prognostic marker in CLL, equivalent to that of IgVH gene mutational status.

Aged↗

Emotional processing and panic.

In this paper Rachman's concept of emotional processing was extended and a model highlighting the psychological operations underpinning processing was specified. Using this model, the aim was to investigate, by means of a questionnaire, whether patients with panic disorder (n=50) have more emotional processing difficulties than two samples of healthy controls (London, n=406; Aberdeen, n=125). The panic disorder group did have significantly more emotional processing difficulties than the control groups, showing a marked tendency to control feelings of anger, unhappiness and anxiety. Three emotional processing dimensions distinguished the panic from the control groups: greater control of emotional experiences ('smothering' or 'bottling up' emotions), greater awareness of feelings and more difficulties in labelling emotions. The authors hypothesise that emotional processing deficits act as a vulnerability factor for developing panic attacks.

Adult↗

A subset of t(11;14) lymphoma with mantle cell features displays mutated IgVH genes and includes patients with good prognosis, nonnodal disease.

We analyzed lymphocyte morphology, histology, immunophenotype, immunoglobulin heavy chain (IgVH) gene mutations, and clinical course in 80 unselected patients presenting with circulating t(11;14) lymphocytes. Of the 80 patients, 43 had peripheral lymphadenopathy (nodal group), and histology confirmed mantle cell lymphoma (MCL) in all. There were 37 patients with no lymphadenopathy (nonnodal group); 13 of 37 had histology, all showing MCL. IgVH genes were unmutated in 28 (90%) of 31 nodal and 15 (44%) of 34 nonnodal cases (P =.0001); CD38 was positive in 32 (94%) of 34 nodal and 16 (48%) of 33 nonnodal cases (P <.001); 41 (95%) of 43 nodal patients required immediate treatment compared with 18 (49%) of 37 nonnodal patients who had indolent disease (P <.0001). Median survival (95% confidence interval) was 30 months (10-50) in the nodal group and 79 months (22-136) in the nonnodal group (P =.005). Mutation status did not statistically affect survival, but of 6 long-term survivors (> 90 months) all were nonnodal and 5 of 5 had mutated IgVH genes. Lymphocyte morphology was heterogeneous in both groups: typical MCL in 56 cases (34 nodal, 22 nonnodal), blastoid MCL in 8 cases (3 nodal, 5 nonnodal), and small-cell MCL in 16 cases (6 nodal, 10 nonnodal, P =.12). Matutes immunophenotyping score was 1 in 65 cases and 2 in 15 (8 nodal, 7 nonnodal). We find no evidence against a diagnosis of MCL in the nonnodal group and suggest that mutated IgVH genes may help identify patients with indolent disease.

ADP-ribosyl Cyclase↗

Effects of multi-sensory stimulation for people with dementia.

BACKGROUND: Over recent years multi-sensory stimulation (MSS) has become an increasingly popular approach to care and is used in several centres throughout Europe. This popularity could be explained by the limited alternatives available to staff and a widely held belief that MSS is a friendly and highly humane approach. A randomized controlled trial was therefore essential to evaluate the effectiveness and extent of the benefits of MSS. AIM: To assess whether MSS is more effective in changing the behaviour, mood and cognition of older adults with dementia than a control of activity (playing card games, looking at photographs, doing quizzes, etc.). METHODS: A total of 136 patients from three countries [United Kingdom (UK), the Netherlands and Sweden] were randomized to MSS or activity groups. Patients participated in eight 30-minute sessions over 4 weeks. Ratings of behaviour and mood were taken before, during and after sessions to investigate immediate effects. Pre-, mid-, post-trial and follow-up assessments were taken to investigate any generalization of effects to cognition and behaviour and mood at home/on the ward or at the day hospital. RESULTS: There were limited short-term improvements for both the MSS and activity groups immediately after sessions, and limited short-term improvements between the groups during sessions. There were no significant differences between the groups when assessing change in behaviour, mood or cognition at home/on the ward or at the day hospital. In the UK, however, behaviour at the day hospital for both groups remained stable during the trial but deteriorated once the sessions had stopped, and active/disturbed behaviour at home improved but likewise deteriorated once sessions had stopped. CONCLUSIONS: Overall, MSS was found to be no more effective than an activity in changing the behaviour, mood or cognition of patients with dementia in the short- or long-term.

Acoustic Stimulation↗

Is the risk of adult coeliac disease causally related to cigarette exposure?

OBJECTIVE: Previous studies have shown an association between cigarette smoking and coeliac disease, but it has yet to be established whether this relationship is causal. The aim of this study was to assess causality using the Bradford Hill criteria. METHODS: A matched case-control study using a questionnaire to establish a detailed smoking history for 138 incident cases of adult coeliac disease and 276 age-matched and sex-matched controls. Subjects were categorized according to their active cigarette exposure prior to diagnosis of the matched case, and odds ratios and tests for linear trends were calculated. RESULTS: At the time of diagnosis, 10% of cases and 30% of controls were current smokers (odds ratio, 0.21 and 95% confidence interval, 0.11-0.40 for coeliac disease in current smokers versus never smokers). A biological gradient was demonstrated for total, recent and current cigarette exposure. The greatest risk reduction related to current exposure (odds ratio, 0.15, and 95% confidence interval, 0.06-0.37 for coeliac disease in current heavy smokers versus never smokers). CONCLUSIONS: This study strengthens the case for a causal relationship between smoking and coeliac disease by demonstrating a strong, temporally appropriate and dose-dependent effect, thus meeting the Bradford Hill criteria. This suggests that cigarette smoking truly protects against the development of adult coeliac disease.

Adult↗

Multivariate analysis of prognostic factors in CLL: clinical stage, IGVH gene mutational status, and loss or mutation of the p53 gene are independent prognostic factors.

This study evaluates the prognostic significance of genetic abnormalities (detected at or shortly after presentation), clinical stage, lymphocyte morphology, CD38 expression, and IGVH gene status in 205 patients with chronic lymphocytic leukemia (B-CLL). Deletion of chromosome 11q23, absence of a deletion of chromosome 13q14, atypical lymphocyte morphology, and more than 30% CD38 expression are significantly associated with the presence of unmutated IGVH genes. Advanced stage, male sex, atypical morphology, more than 30% CD38 expression, trisomy 12, deletion of chromosome 11q23, loss or mutation of the p53 gene, and unmutated IGVH genes are all poor prognostic factors in a univariate analysis. However, only 98% or more homology of IGVH genes to the germline sequence, loss or mutation of the p53 gene, and clinical stage retain prognostic significance in a multivariate analysis. The median survival of patients with mutated IGVH genes, unmutated IGVH genes, and loss or mutation of the p53 gene regardless of IGVH gene status is 310, 119, and 47 months, respectively. These data should facilitate the design of new trials for the management of patients presenting with advanced disease or poor prognosis early stage disease.

ADP-ribosyl Cyclase↗

CD38 expression and immunoglobulin variable region mutations are independent prognostic variables in chronic lymphocytic leukemia, but CD38 expression may vary during the course of the disease.

Although the presence or absence of somatic mutations in the immunoglobulin variable region (IgV(H)) genes in chronic lymphocytic leukemia (B-CLL) identifies subtypes with very different prognoses, the assay is technically complex and unavailable to most laboratories. CD38 expression has been suggested as a surrogate marker for the 2 subtypes. IgV(H) mutations and CD38 expression in 145 patients with B-CLL with a long follow-up were compared. The 2 assays gave discordant results in 41 patients (28.3%). Multivariate analysis demonstrated that Binet stage, IgV(H) mutations and CD38 were independent prognostic indicators. Median survival time in patients whose cells had unmutated IgV(H) genes and expressed CD38 was 8 years; in those with mutated IgV(H) genes not expressing CD38, it was 26 years. For those with discordant results, median survival time was 15 years. Thus, although CD38 expression does not identify the same 2 subsets as IgV(H) mutations in CLL, it is an independent risk factor that can be used with IgV(H) mutations and clinical stage to select patients with B-CLL with the worst prognoses. Using cryopreserved cells taken at intervals during the course of the disease, however, changes of CD38 expression over time were demonstrated in 10 of 41 patients. Causes of the variation of CD38 expression require further study. Additional prospective studies are required for comparing CD38 expression with other prognostic factors and for taking sequential measurements during the course of the disease.

ADP-ribosyl Cyclase↗