阿尔茨海默病者的早期眼球跟踪运动缺失

The aim of this study is to evaluate pursuit ocular movements (POM) provided by a vision-based non-intrusive eye tracker in patients with early Alzheimer disease (AD). Oculomotor performance has not been extensively studied in AD. Studies to date have been consistent in reporting poor performance in AD patients. In fact, previous studies suggest that patients affected by AD have clear alterations of smooth-pursuit ocular movements induced by a predictable target. Values of POM were lower in AD patients than in NC (p<0.001). In AD patients, values didn’t correlated closely with MMSE scores (p=0.3). No significant differences were found in AD patients treated with different medications. We used a vision-based method, under pending patent, for non-intrusive eye tracking, previously described, which can be proposed as a possible tool for supporting the diagnosis of early AD, in association with clinical evaluation, as an add-on to the neuropsychological scores.     

Relationship between body mass index and insulin resistance in patients treated with second generation antipsychotic agents

Second generation antipsychotics (SGAs) can increase weight gain and weight-induced insulin resistance. Recent studies have suggested weight-independent effects of certain SGAs on insulin resistance; however the magnitude of these effects and the relationship between BMI and insulin resistance in patients on SGAs are not established. To evaluate, the relationship between body mass index (BMI) and insulin resistance in 54 patients being stably treated with olanzapine (n = 19), risperidone (n = 16), or aripiprazole (n = 19) was compared with data from a large reference population (n = 201) not on SGAs. Insulin resistance was directly quantified by measuring the steady-state plasma glucose (SSPG) concentration during the insulin suppression test. The relationship between BMI and SSPG was similar between the SGA (r = 0.58) and the reference population (r = 0.50). When SSPG was standardized based on expected values for the reference population, patients on olanzapine had a higher degree of insulin resistance (mean z-score ± SD, 0.68 ± 0.9) than expected for level of BMI compared with those on aripiprazole (−0.25 ± 1) and risperidone (−0.3 ± 0.9), F(2, 51) = 6.28 (p = 0.004). Thus, olanzapine group was 0.76 SD above the reference population or in the 78 percentile for insulin resistance. SSPG was correlated with fasting plasma insulin concentration (0.78 (0.64-0.87), p < 0.001) but not fasting glucose concentration (0.15 (−0.13-0.40), p = 0.29). In conclusion, BMI contributes a quarter to a third of the variance in insulin resistance in the SGA population similar to the reference population. Olanzapine also appears to have an independent effect on insulin resistance that is above and beyond obesity.     

Treatment with beta-erythropoietin in lung cancer--effectiveness and quality of life improvement in clinical practice

Anemia is common among patients with malignant tumors, due to the disease and chemotherapy. Anemia decreases patient's quality of life, and worsens the dose-intensity of chemotherapy. The aim of this retrospective data-analysis was to evaluate quality of life and hemoglobin levels in 19 consecutive lung cancer patients receiving beta-erythropoietin, due to chemotherapy induced anemia. A self developed, patient source data based quality of life questionnaire was used. The mean pre-erythropoietin hemoglobin concentration of the patients was 96.31±6.72 g/L (mean±SD), the post-treatment hemoglobin concentration 111.63±14.05 g/L (p<0.05). During the chemotherapy of the 19 patients with lung cancer, transfusion was given only four times. The mean quality of life total score of the patients increased significantly during erythropoietin treatment that was resulted by the improvements of scores determining dizziness, tachycardia, and fatigue. Main limitations of this real life data analysis are low patient number and the lack of validation in the used questionnaire. In summary, according to our experiences, the use of beta-erythropoietin in patients with lung cancer results improved quality of life and a low rate of transfusions.     

Biomarkers and personalized medicine: current status and further perspectives with special focus on dermatology

Biomarkers are of increasingly high importance in medicine, particularly in the realm of ‘personalized medicine’. They are valuable for predicting prognosis and dose selection. Moreover, they may be helpful in detecting therapeutic and adverse responses and in patient stratification based on efficacy or safety prediction. Thus, biomarkers are essential tools for the selection of appropriate patients for treatment with certain drugs to and enable personalized medicine, that is ‘providing the right treatment to the right patient, at the right dose at the right time’. Currently, there are six drugs approved for dermatological indications with recommended or mandatory biomarker testing. Most of them are used to treat melanoma and human immunodeficiency virus infection. In contrast to the few fully validated biomarkers, many exploratory biomarkers and biomarker candidates have potential applications. Prognostic biomarkers are of particular significance for malignant conditions. Similarly, diagnostic biomarkers are important in autoimmune diseases. Disease severity biomarkers are helpful tools in the treatment for inflammatory skin diseases. Identification, qualification and implementation of the different kinds of biomarkers are challenging and frequently necessitate collaborative efforts. This is particularly true for stratification biomarkers that require a companion diagnostic marker that is co‐developed with a certain drug. In this article general definitions and requirements for biomarkers as well as for the impact of biomarkers in dermatology are reviewed and opportunities and challenges are discussed.     

Genotype–phenotype associations in filaggrin loss‐of‐function mutation carriers

Background. Loss‐of‐function mutations in the filaggrin gene (FLG) have been reported to be associated with specific phenotypic characteristics such as hyperlinearity and keratosis pilaris. Objectives. To study phenotypic features in patients with occupational irritant contact eczema of the hands in relation to FLG loss‐of‐function mutations. Materials and methods. In a prospective cohort study, genotype was determined for 459 study subjects for four FLG null alleles, and investigated for selected history, clinical and laboratory features. Results. Overall, 68 patients showed a mutation in the FLG alleles R501X, R2447X, S3247X, and/or 2282del4. Flexural eczema, xerosis cutis, pityriasis alba, dirty neck, pulpitis sicca, hyperlinear palms, keratosis pilaris and family history of eczema were positively associated with FLG mutations (p < 0.05). Although we observed a statistically significant correlation with higher serum IgE in FLG mutation carriers, allergic rhinoconjunctivitis and allergic asthma were not over‐represented in this group. Conclusion. This study shows further genotype–phenotype correlations in patients with occupational irritant contact eczema and FLG mutation carrier status. These features may help to identify those with FLG mutations on a specific phenotype basis.     

CD26 expression in mature B‐cell neoplasia: its possible role as a new prognostic marker in B‐CLL

CD26 (dipeptidyl peptidase IV, DPP IV) is widely expressed by T and natural killer (NK) cells, epithelial and endothelial cells of different tissues, and it is strongly upregulated in activated B‐cells; moreover it plays a regulatory role in the neoplastic transformation and progression of various types of tumours. CD26 expression was evaluated by means of flow cytometry in various peripheral B‐cell lymphoid tumours: 12 follicular and 12 mantle cell lymphomas, 20 multiple myelomas (MMs), 12 hairy cell leukaemias (HCLs), 112 chronic lymphocytic leukaemias (CLLs), 20 CD5^negative B‐cell chronic lymphoproliferative diseases (CD5^neg B‐CLPDs) and 12 diffuse large cell lymphomas (DLCLs). CD26 expression was absent or barely detectable in follicular and mantle cell lymphomas, high in MMs and HCLs, and variable in CLLs, in CD5^neg B‐CLPDs and in DLCLs. CD26 significantly correlated with CD49d and CD38 expressions (p < 0.0001) in B‐CLLs, and there was a significant correlation between CD26 and ZAP‐70 expressions or IgVH mutational status (p < 0.0001). After a median follow‐up of 36 months, 65 B‐CLL patients were treated; taking 10% as the best CD26 cut‐off value, Kaplan–Meier curves revealed a significantly shorter time to treatment in the CD26‐positive cases (p < 0.0001). Overall, our data indicate that CD26 expression may identify subsets of B‐CLL patients with an unfavourable clinical outcome in terms of therapeutic need, thus suggesting its potential role as a marker (together with CD38 and CD49d) in a future routine cytofluorimetric panel to be validated for the prognostic stratification of B‐CLLs. Copyright © 2009 John Wiley & Sons, Ltd.