Physical activity in chronic home-living and sub-acute hospitalized stroke patients using objective and self-reported measures

Background: Despite confirmed reduced physical activity (PA) after stroke in various stages of recovery, the type of activities stroke patients executed and the time spent at different activity levels have not been sufficiently verified with stroke-validated assessment tools.

Design: Observational study.

Objective: To determine PA of sub-acute stroke patients hospitalized in a rehabilitation centre (HOS) compared to chronic home-living stroke patients (HOM) using objective and self-reported measures during 2 weekdays and 1 weekend day.

Methods: Fifteen HOS and 15 HOM patients wore a Sense Wear Pro 2 accelerometer (METs*minutes/24 h) and a knee-worn pedometer Yamax Digi Walker SW 200 (steps) and filled in a coded activity diary (kcal/24 h; METs*minutes/24 h) during three consecutive days.

Results: In HOM significantly more steps (steps_{total HOM} = 18722.6 ± 10063.6; steps_{total HOS} = 7097.8 ± 5850.5) and higher energy expenditure (EE) levels (EE_{total HOM} = 7759.34 ± 2243.04; EE_{total HOS} = 5860.15 ± 1412.78) were measured. In this group less moderate activity (≥3–6 ≤ METs) was performed on a weekday (p_day1 = 0.006; p_day2 = 0.027) and in total (p = 0.037). Few therapy hours (physical, occupational and speech therapy, and psychological support) were provided in HOM compared to HOS (p < 0.001). Vigorous activities were only seen in HOM. In both groups few patients executed sport activities.

Conclusions: In HOM significantly more steps were performed and higher EE values were measured. However, participation in moderate activities and time spent on therapy were less in HOM. Evaluating PA with quantitative measures is feasible in both chronic home-living and sub-acute hospitalized patients with stroke.     

Is melatonin helpful in stopping the long-term use of hypnotics? A discontinuation trial

Objective To find out if administration of melatonin facilitates discontinuation of benzodiazepine (BD) therapy in patients with insomnia. Method A placebo controlled trial in nine general practices in the Netherlands. Long-term users of benzodiazepines were asked by their GP to participate in a discontinuation program in combination with melatonin or placebo. The intervention and follow-up period lasted one year. During this period participants received four questionnaires about their use of sleeping medication and several health instruments. The urine of all participants was tested for the presence of benzodiazepines, as proof of the discontinuation. Main outcome measure The discontinuation of benzodiazepine use measured by questionnaires and urine samples at three assessment points. Results A total of 503 long-term users were selected by the GPs, of whom 38 patients (16M/22F) participated. After one year 40% had stopped their benzodiazepine use, both in the intervention group on melatonin and in the placebo control group. Comparing stoppers and non-stoppers did not reveal significant differences in benzodiazepine use, or awareness of problematic use. Conclusion Our findings do not conclusively indicate that melatonin is helpful for the discontinuation of the use of benzodiazepines, but the average dose of benzodiazepines in the group was low. Further investigation is necessary, with special attention to the possible influence of the daily dose on the facilitation effect of melatonin. Frans H. J. A. Vissers passed away in September 2006     

The topical treatment of psoriasis

According to the patients, improvement of efficacy, long-term safety and improvement of compliance are needed. The topical treatment has been innovated during the last decade. Most important are the introduction of two new classes of treatments: topical vitamin D(3) analogues and the retinoid tazarotene. To what extent, however, have we achieved developments which are in line with the needs as expressed by the patients? Improved efficacy has been realized by successful combinations of topical treatments. In particular, the combinations of dithranol, vitamin D(3) and tazarotene with a topical corticosteroid proved to be very effective with a reduced profile of side-effects. The efficacy of vitamin D(3) analogues and tazarotene is such that the efficacy of a potent corticosteroid (betamethasone-17-valerate) is approached; calcipotriol even showed an efficacy which is at least as good as this corticosteroid. The long-term safety of new compounds has been evaluated for at least 12 months in large studies. Remarkably for corticosteroids such information is available for only 12 weeks. However, intermittent applications of a topical corticosteroid in combination with another topical treatment provide an effective and safe long-term control of psoriasis. Compliance is a conditio sine qua non for an effective topical treatment. Important progress has been made to increase compliance. Short-contact dithranol has been popularized as an ambulatory treatment which is a highly effective approach as a care instruction programme. Formulations which are better from a cosmetical point of view have been developed for various topical treatments. Reduction of the frequency of applications proved to be possible for most treatments. Once daily applications for corticosteroids, vitamin D(3) analogues and retinoids have been developed, and intermittent applications, a few times per week, are possible for corticosteroids, which proved to be very effective with a reduced profile of side-effects, and are also developed for dithranol.     

Dendritic cells break tolerance and induce protective immunity against a melanocyte differentiation antigen in an autologous melanoma model

Tyrosinase-related protein (TRP) 2 belongs to the melanocyte differentiation antigens and has been implicated as a target for immunotherapy of human as well as murine melanoma. In the current report, we explored the efficacy of nonmutated epitopes with differential binding affinity for MHC class I, derived from mouse TRP2 to induce CTL-mediated, tumor-reactive immunity in vivo within the established B16 melanoma model of C57BL/6 mice. The use of nonmutated TRP2-derived epitopes for vaccination provides a mouse model that closely mimics human melanoma without introduction of xenogeneic or otherwise foreign antigen. The results demonstrate that vaccination with TRP2 peptide-loaded bone marrow-derived dendritic cells (DCs) results in activation of high avidity TRP2-specific CTLs, displaying lytic activity against both B16 melanoma cells and normal melanocytes in vitro. In vivo, protective antitumor immunity against a lethal s.c. B16 challenge was observed upon DC-based vaccination in this fully autologous tumor model. The level of protective immunity positively correlated with the MHC class I binding capacity of the peptides used for vaccination. In contrast, within this autologous model, vaccination with TRP2 peptide in Freund's adjuvant or TRP2-encoding plasmid DNA did not result in protective immunity against B16. Strikingly, despite the observed CTL-mediated melanocyte destruction in vitro, melanocyte destruction in vivo was sporadic and primarily restricted to minor depigmentation of the vaccination site. These results emphasize the potency of DC-based vaccines to induce immunity against autologous tumor-associated antigen and indicate that CTL-mediated antitumor immunity can proceed without development of adverse autoimmunity against normal tissue.     

Molecular cloning and immunogenicity of renal cell carcinoma-associated antigen G250

The molecular cloning of the cDNA and gene encoding the renal cell carcinoma (RCC)-associated protein G250 is described. This protein is one of the best markers for clear cell RCC: all clear-cell RCC express this protein, whereas no expression can be detected in normal kidney and most other normal tissue. Antibody studies have indicated that this molecule might serve as a therapeutic target. In view of the induction/up-regulation of G250 antigen in RCC, its restricted tissue expression and its possible role in therapy, we set out to molecularly define the G250 antigen, which we identified as a transmembrane protein identical to the tumor-associated antigen MN/CAIX. We determined, by FISH analysis, that the G250/MN/CAIX gene is located on chromosome 9p12-13. In view of the relative immunogenicity of RCC, we investigated whether the G250 antigen can be recognized by TIL derived from RCC patients. The initial characterization of 18 different TIL cultures suggests that anti-G250 reactivity is rare.     

Interphase cytogenetics of prostatic adenocarcinoma and precursor lesions: Analysis of 25 radical prostatectomies and 17 adjacent prostatic intraepithelial neoplasias

Twenty-five radical prostatectomy specimens were screened for the presence of numerical chromosome changes within the adenocarcinoma as well as in 17 adjacent prostatic intraepithelial neoplasias (PIN) by means of interphase in situ hybridization (ISH) to routinely processed tissue sections. To this end a defined alfoid repetitive DNA probe set was used, specific for the centromeres of chromosomes 1, 7, 8, 10, 15, and Y. The cytogenetic information was correlated with histopathological and clinical features as well as with DNA ploidy. Numerical aberrations of at least one chromosome were shown in 13 of 25 cases (52%). Alterations of chromosome 8 and loss of the Y chromosome were the most frequent findings (both 20%), followed by loss of chromosomes 15 (16%) and 10 (12%). Gain of chromosome 7 was seen in 8% of cases. No aberrations of chromosomes 7, 8, 10, and 15 were found in the adjacent PIN lesions, whereas loss of the Y chromosome in both PIN and tumor occurred in two cases. Also, (low level) aneuploidy was observed in 76% of these PIN lesions. Ploidy of the carcinomas as assessed by ISH correlated well with ploidy measured by DNA flow cytometry (FCM; P < 0.02). Due to the more specific correspondence between ISH and tumor pathology, pathologic grade correlated with ISH aneuploidy (P < 0.05), whereas FCM ploidy did not. Furthermore, genetic heterogeneity within a tumor was seen, as judged by the focal appearance of chromosomal aberrations. Chromosomal alterations occurred in all grades and stages, although loss of chromosome 10, gain of chromosome 7, and aberrations of chromosome 8 tended to predominate in more advanced cancers.     

Established treatments of psoriasis

Psoriasis is a complex disease with a spectrum of clinical manifestations. Psoriasis may express as a few coin-sized erythemato-squamous plaques up to widespread disease covering the entire body surface (erythrodermic psoriasis). Psoriasis may present as a few stable plaques or unstable disease, rapidly relapsing after treatment. Some patients may respond excellently to topical treatments whereas other patients may be difficult to manage, showing treatment resistance even to the systemic treatments. Therefore, a spectrum of treatments is available to individualize care of psoriasis. In this chapter the available treatments are presented. The vast majority of patients is treated with topical treatments, with vitamin D(3)analogs and topical corticosteroids as the first line treatments. Tazarotene is an alternative for vitamin D(3) treatment if this treatment fails. In some special cases, dithranol and tar treatment may be used. Phototherapy with UVB and photochemotherapy (PUVA) are indicated in patients not responding sufficiently to topical treatment. However, chronic exposure, in particular to photochemotherapy implies an increased risk for photo- carcinogenicity. Systemic treatments including methotrexate, cyclosporin, acitretin and fumarates are indicated in patients who cannot be managed with topical treatments or phototherapy, either for treatment resistance or cumulative toxicity. In this article the opportunities and limitations of the available treatments are presented.     

BLC (CXCL13) is expressed by different dendritic cell subsets in vitro and in vivo

Dendritic cells (DC) attract both T and B lymphocytes to induce an efficient antigen-specific immune response. Recently, it was shown that na?ve T cells are attracted to DC by dendritic cell chemokine 1 (DC-CK1, CCL18). The potent B lymphocyte chemoattractant BLC (CXCL13) was previously shown to be essential for homing of lymphocytes into secondary lymphoid organs and for the development of B cell follicles. As the cells that produce BLC are largely unknown and BLC could be a candidate chemokine for the recruitment of B cells to DC, we analyzed different DC subsets for expression of BLC. Here we demonstrate that monocyte-derived DC as well as activated blood DC indeed express and secrete BLC. Interestingly, ligation of the CD40 molecule down-regulated BLC expression in monocyte-derived DC. Staining of tonsilar sections indicated that BLC is expressed by follicular dendritic cells and germinal center dendritic cells (GCDC) in vivo. Real-time quantitative PCR confirmed the expression of BLC in isolated GCDC. Since both B cells and activated T cells express the receptor for BLC, our findings implicate an important role for BLC in establishing the interaction of DC with T cells and B cells. Furthermore, CD40/CD40 ligand interactions could modulate this process by down-regulating the expression of BLC.