LOPP alternating with EVAP is superior to LOPP alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation trial.

PURPOSE: The purpose of this randomized trial was to compare the efficacy of eight cycles of chlorambucil, vincristine, procarbazine, and prednisone (LOPP) with four cycles of LOPP that alternate with four cycles of etoposide, vinblastine, Adriamycin (doxorubicin; Familitalia Carlo Erba, Ltd, UK), and prednisone (EVAP) in patients with advanced Hodgkin's disease. PATIENTS AND METHODS: Between June 1983 and December 1989, 594 patients were entered onto the study. Of the 594, 295 patients were allocated to receive LOPP, and 299 were allocated to receive LOPP/EVAP. RESULTS: The complete remission (CR) rates were 57% and 64%, respectively, after initial chemotherapy (difference not significant [NS]), and 65% and 75%, respectively, after the subsequent administration of radiotherapy to residual masses (P less than .01). The procedure associated mortality in the LOPP and LOPP/EVAP arms was 1% and 3%, respectively. The actuarial CR relapse-free survival was significantly greater in the LOPP/EVAP arm (P less than .001) as was the overall survival (P less than .05). The CR relapse-free rate, disease-free survival (DFS) rate, and overall survival rate at 5 years were 52%, 32%, and 66%, respectively, in the LOPP arm, compared with 72%, 47%, and 75% in the LOPP/EVAP arm, respectively. CONCLUSION: These results indicate that LOPP and EVAP is superior to LOPP alone as initial treatment for advanced Hodgkin's disease.     

Effectiveness of telephone counseling for mammography: results from five randomized trials.

BACKGROUND: Women over age 50 continue to be underscreened for breast cancer. The purpose of this report is to compare the effectiveness of a barrier-specific telephone counseling intervention across the five study sites of the Breast Cancer Screening Consortium (BCSC). METHODS: Each of the BCSC projects was a randomized study of the effectiveness of telephone counseling (TC) in comparison to a control condition. Eligible underusers were identified and surveyed by telephone before and after the implementation of the interventions. Data from a total of 3,461 underusers were analyzed. We tested whether significantly more women randomized to TC than to control were regular mammography users at the follow-up survey. Data were analyzed separately by site. RESULTS: Overall, TC was not significantly more effective than control in encouraging regular mammography. The pooled consortium-wide odds ratio was 1.08 (95% confidence interval: 0.91 to 1.27). CONCLUSIONS: TC has the potential to support maintenance of mammogram use. Modifications are needed to maximize this potential and additional methods should be used in conjunction with TC to reach women who are underusers of mammography.     

Analysis of glutathione <Emphasis Type="Italic">S</Emphasis>-transferase Pi isoform (GSTP1) single-nucleotide polymorphisms and macular telangiectasia type 2

Recent imaging studies have suggested that macular pigment is decreased centrally in macular telangiectasia type 2 (MT2). The uptake of xanthophyll pigment into the macula is thought to be facilitated by a xanthophyll-binding protein (XBP). The Pi isoform of glutathione S-transferase (GSTP1) represents one such XBP with high binding affinity. This case–control study aimed to determine whether two common single-nucleotide polymorphisms (SNPs) of GSTP1 were associated with MT2. DNA samples from 39 cases and 21 controls were collected. Two polymorphic sites of Ile105Val and Ala114Val in exons 5 and 6 respectively, of the GSTP1 gene were analysed. Comparison of alleles and genotypes between cases and controls indicated that there were no statistically significant differences for either the Ile105Val SNP (P = 0.43) or the Ala114Val SNP (P = 0.85), or for any combinations; however, the homozygous at-risk genotype (GG) of the Ile105Val SNP was present in 8% of cases but absent in controls. This study found no statistically significant association between two common GSTP1 SNPs and MT2; however, a trend towards a greater frequency of the GG genotype of the Ile105Val SNP in cases is of great interest. The biological plausibility of disturbed macular pigment uptake in MT2 makes GSTP1 an excellent candidate gene. Further investigation is warranted in future studies of MT2.     

Comparison of alterations in c-fos and Egr-1 (zif268) expression throughout the rat brain following acute administration of different classes of antidepressant compounds.

The majority of immediate-early gene (IEG) studies focus on a few key brain regions associated with the class of psychoactive compound being studied. Recently, using a meta-analysis of the c-fos literature, we demonstrated the utility of c-fos profiling to classify such compounds. The present study examined acute delivery of a range of antidepressant classes; fluoxetine, imipramine, LiCl, and mirtazapine. The dual aims were to study the IEG profiles of these varying classes of antidepressants throughout the rat brain and to compare the utility of c-fos or Egr-1 as IEGs to classify clinically efficacious antidepressants. All antidepressants increased c-fos mRNA in the central amygdala, as previously shown, while c-fos was also increased in the anterior insular cortex and significantly decreased within the septum. Although acute antidepressant administration altered c-fos expression in a number of brain regions, Egr-1 expression was only significantly altered in the central amygdala, suggesting that Egr-1 may not be as useful a marker to investigate acute antidepressant treatment. The fact that these drugs, including the previously unclassified antidepressant mirtazapine, share a number of common loci of activation, which are implicated by human and animal studies in depression, adds further support to the use of IEG mapping to classify psychoactive compounds.     

Psychometric Assessment of Dynamic Risk Factors for Child Molesters

To explore the relationship between dynamic risk factors and recidivism in child molesters, we studied a sample of men (N=495) who completed an intensive, prison-based treatment program in New Zealand. During the follow-up period (M=5.8 years), 9.9% were reconvicted for a sexual offense. A self-report psychometric battery was administered at pre-treatment that assessed a range of variables related to sexual attitudes and beliefs, emotional functioning, and interpersonal competency. Factor analysis showed that individual differences in the battery could be described by four dimensions-Social Inadequacy, Sexual Interests, Anger/Hostility, and Pro-Offending Attitudes. Factor scores for each dimension were significantly correlated with sexual recidivism. Logistic regression analyses confirmed that the Sexual Interests and Pro-Offending Attitudes factor scores, as well as an Overall Deviance score which combined the dimensions, provided significant additional validity for predicting recidivism beyond the Static-99 (Hanson and Thornton Law and Human Behavior 24:119-136, 2000). When added to the Static-99, the Overall Deviance score increased the area under the Receiver-Operating Characteristic curve (AUC) from 0.72 to 0.81. These results show that psychometric self-reports can provide valid measures of dynamic risk factors, and that inclusion of such measures can improve risk prediction beyond that achievable by static factors alone.     

General practice: a leading provider of medical student education in the 21st century?

General practice is well placed to become a major setting for medical student education over the next decade. New models of clinical education are required, to take account of changes in the patient population, disease profile and management strategies. While there has been an increase in general practice-based and other community-based education, there is the potential for further expansion. Evidence for the positive role of general practitioners and general practice in medical education is growing, including the benefits of prevocational training in general practice. If GPs are to assume a major role in community-based education of medical students, there will need to be changes in funding structures and supporting resources, particularly at this time of increasing medical student numbers and workforce shortage and maldistribution.