The development of targeted chemotherapy for CNS lymphoma—a pilot study of the IDARAM regimen

Purpose We have developed and evaluated a CNS-targeted chemotherapy regimen based on the pharmacokinetic properties of the individual drugs in the combination.Patients and methods In a twin-track study, 16 patients with secondary CNS lymphoma (SCNSL) and 8 with primary CNS lymphoma (PCNSL) were treated with IDARAM which comprised idarubicin 10 mg/m² i.v., days 1 and 2; dexamethasone 100 mg, 12-h infusion, days 1, 2 and 3; cytosine arabinoside (ARA-C) 1.0 g/m², 1-h infusion, days 1 and 2; methotrexate 2.0 g/m², 6-h infusion, day 3 (with folinic acid rescue); and cytosine arabinoside 70 mg plus methotrexate 12 mg, intrathecally, days 1 and 8. Two cycles were delivered at 3-weekly intervals. After response assessment, patients received adjuvant cranial radiotherapy (40 Gy over 20 fractions).Results The series comprised 24 patients, 11 male and 13 female. Their median age was 53 years (range 21 to 73 years). Grade 4 neutropenia and thrombocytopenia occurred in the majority of patients treated. Of the eight PCNSL patients, seven achieved complete remission (CR). Four remained in CR at the time of this report with a median duration of follow-up of 25 months (range 11 to 42 months). Of the 16 SCNSL patients, 12 achieved CR. Seven patients remained in CR at the time of this report with a median duration of follow-up of 24 months (range 18 to 57 months).Conclusion This study suggests that IDARAM is an effective regimen in both PCNSL and SCNSL and is suitable for further development and evaluation.This work is presented on behalf of the Central and Southern Lymphoma Group.     

Illness behavior and social support in patients with chronic venous ulcers

Venous ulcers are a chronic and costly condition for providers and payors, as well as for patients, particularly the elderly. To examine the association between chronic venous ulceration, illness behavior, and levels of social support, patients drawn from a separate clinical trial (N = 74) were interviewed using the Illness Behaviour Questionnaire and the Social Support Questionnaire. Results indicate that women had higher hypochondriasis (1.70 versus 1.03, P = 0.19), affective disturbance (2.70 versus 1.42, P = 0.08), and number of supports (Social Support Questionnaire, 2.41 versus 1.81, P = 0.056) than men, although no score achieved a standard level of statistical significance. Patients under 70 years of age had significantly higher hypochondriasis (1.96 versus 1.17, P = 0.021) and irritability (1.38 versus 0.90, P = 0.026) scores than those older than 70 years, although denial was significantly higher in those older than 70 years (3.97 versus 3.46, P = 0.045). The level of satisfaction with social support was significantly higher in those under 70 years of age (5.13 versus 4.97, P = 0.042). These results underscore the psychological and social cost imposed by chronic venous ulceration on older women. They also support previous studies implying a greater psychological burden on younger patients. The association between illness behavior and social support remains unclear, but examining the association between illness behavior and social support among patients with venous ulceration provides an opportunity to increase understanding of the psychological, physical, and social dynamics of this chronic condition.     

Effects of oral prednisolone on biomarkers in synovial tissue and clinical improvement in rheumatoid arthritis

OBJECTIVE: To create greater understanding of the changes in synovial tissue parameters that occur in conjunction with clinical response by using an effective therapy, in order to facilitate the planning of future studies with therapeutic agents for rheumatoid arthritis (RA). METHODS: Twenty-one patients with active RA were randomized to receive either oral prednisolone (n = 10) or placebo (n = 11) for 2 weeks. In all patients, synovial tissue biopsy specimens were obtained by arthroscopy directly before treatment and after 14 days of treatment. Immunohistochemical analysis was performed to characterize the cell infiltrate and vascularity. Stained tissue sections were analyzed by digital imaging. Statistical analysis was performed using an analysis of covariance model. RESULTS: After treatment, the mean Disease Activity Score in 28 joints (DAS28) was 2.0 units lower (95% confidence interval [95% CI] 1.0-3.0) in patients who received prednisolone than in those who received placebo. In the prednisolone group, the mean (+/-SD) DAS28 decreased from 6.27 +/- 0.95 to 4.11 +/- 1.43 after therapy; minimal change was observed in the placebo group. For macrophages, the estimated effect of prednisolone was large. Patients receiving active treatment had fewer (mean 628 cells/mm(2) [95% CI 328-927]) macrophages after therapy compared with those receiving placebo. A reduction in the total number of CD68+ macrophages, from 1,038 +/- 283 cells/mm(2) before treatment to 533 +/- 248 cells/mm(2) after treatment, was observed in the prednisolone group. There were clear trends toward decreased infiltration by T cells, plasma cells, and fibroblast-like synoviocytes after active treatment. We observed a trend toward a reduction in alphavbeta3+ newly formed blood vessels and expression of vascular growth factors after prednisolone therapy. CONCLUSION: Prednisolone therapy in RA is associated with a marked reduction in macrophage infiltration in synovial tissue, suggesting that synovial macrophage numbers could be used as a biomarker for clinical efficacy.     

Prevalence of psychiatric disorder in Europe: the potential and reality of meta-analysis

Abstract. Background: Within the European Mental Health Status Project, over 200 psychiatric surveys concerning members of the European Union (plus Norway) were examined for their potential for meta-analysis with regard to prevalence of psychiatric disorders and basic demographic and social variables. The diversity of samples, methods, analysis and presentation was such that only data derived from GHQ-12 and CIDI studies could be used, and those relating to sex differentials only. Methods: The statistical program Stata was used to compute odds ratios (with confidence intervals) for individual studies, and to produce fixed and random effects estimates of the pooled odds ratio for all studies together, and a measure of heterogeneity. Forrest Plots were also produced. Results: Analysis of GHQ-12 data with a cut-off point of 4, indicating a current or recent probable mental health problem, showed, as expected, that women had higher prevalence rates than men. However, there was a relatively high heterogeneity score, suggesting that these studies may not be measuring the same thing. Analysis of CIDI results showed homogeneity for major depressive disorder within the last 12 months, with the risk for men about half of that for women. Conclusions: In terms of advancing epidemiological knowledge, the results are trivial, at most confirming what is already well known. However, the study shows the potential for pooled analysis, with much greater power in epidemiological investigation if consistency could be achieved in research. Various ways in which this might be done are discussed. It also shows the value of personal knowledge and personal networks in fields which are not well handled by electronic literature databases.An erratum to this article can be found at     

Fast onset of dopamine uptake inhibition by intravenous cocaine

In vivo voltammetry in the nucleus accumbens of anesthetized rats was used to investigate the time of onset of dopamine uptake inhibition by intravenous cocaine. There is disagreement between behavioral and neurochemical studies concerning the time-course of cocaine effects. Because of the high temporal resolution of voltammetry, the processes of dopamine release and uptake could be temporally separated to make evaluation of cocaine effects on uptake easier to address. Within 4 s after intravenous cocaine administration (1.5 mg/kg) there was significant inhibition of dopamine uptake that reached a plateau in 20 s. The peak heights of electrically evoked dopamine signals were also rapidly increased by cocaine. The signals returned to baseline values within approximately 1 h. In parallel behavioral studies, locomotor activity was significantly increased within 5-6 s following intravenous infusion of cocaine. Here we demonstrate that intravenous cocaine administration begins inhibiting the uptake of dopamine within a few seconds. This is at least 10-fold faster than previous neurochemical estimates. The present findings may contribute to the understanding of the neurobiological mechanisms underlying the early behavioral responses to cocaine.     

Eczema and the spongiotic dermatoses: a histologic and pathogenic update

The spongiotic dermatoses including eczema and its clinicopathologic variants are capable of presenting in a variety of clinical guises and are pathologically defined by the presence of epithelial intercellular edema that may rarely form blisters. The mechanisms which underlie there pathogensis has only recently begun to be elucidated. Collectively, these disorders comprise an integral facet of dermatology and are the subject of discussion in this article.