Primary cutaneous lymphomas: applicability of current classification schemes (European Organization for Research and Treatment of Cancer, World Health Organization) based on clinicopathologic features observed in a large group of patients.

Classification of primary cutaneous lymphomas (PCLs) is the subject of ongoing controversy. Based on a series of 556 patients, the applicability of the European Organization for Research and Treatment of Cancer (EORTC) classification for PCLs was assessed and compared to the proposed World Health Organization (WHO) classification of hematologic malignancies. The large majority of patients could be properly classified according to the scheme proposed by the EORTC. Comparison of estimated 5-year survival for specific diagnostic categories of PCLs demonstrated nearly complete concordance of the present results with those of the EORTC study for most of the indolent cutaneous T-cell lymphomas and cutaneous B-cell lymphomas, whereas differences were found for mycosis fungoides-associated follicular mucinosis and Sezary syndrome. A few patients with newly described entities (CD8(+) epidermotropic cytotoxic T-cell lymphoma, primary cutaneous natural killer/T-cell lymphoma) could not be classified according to the EORTC scheme. Comparison of the EORTC with the WHO classification showed that the EORTC scheme allows a more precise categorization of the patients, especially for cutaneous B-cell lymphoma. In conclusion, the study confirmed that the EORTC classification allows a better management of patients with PCL. Small amendments to that classification should be carried out to account for recently described entities and to unify some of the diagnostic categories.     

Pulmonary exchange of solutes during experimental lung lavage in pigs

Unilateral continuous lung lavage in a nonregenerating system (3,000 ml isotonic cristalloid) was done in 12 pigs for 270 min. The concentration of substances in serum and fluid was measured. Half-time (t1/2) of exchange and permeability constants (P) were determined. In the fluid Na+ decreased significantly (t1/2 = 107 min, P = 7.8 x 10(-7]. Urea increased significantly, reaching serum level after 270 min (t1/2 = 109.1 min, P = 6.18 x 10(-6]. Ca2+ (t1/2 = 36.7 min, P = 4.1 x 10(-7] PO4 = (t1/2 = 173.3 min, P = 1.1 x 10(-7], and creatinine (t1/2 = 55.2 min, P = 6.2 x 10(-7] also increased markedly but did not reach serum level. The adjustment to serum concentration may be prevented by interaction between diffusion, active transport or Donnan's equilibria. K+ increased almost linearly, documented by the long half-time (t1/2 = 7,835.2 min, P = 7.7 x 10(-7] and did not reach serum level. The calculated limit value was higher than the serum level. Active transport systems or influx of K+ from cellular compartments rather than from the serum might be involved in its linear kinetics. Total protein (t1/2 = 61.5 min, P = 2.06 x 10(-9] and albumin (t1/2 = 58.8 min, P = 1.7 x 10(-9] increased initially but levelled far below the serum value. The low P indicates a lack of significant permeation. Initial increase may be due to washout of the epithelial lining fluid compartment. There was minimal transfer of lavage fluid into the organism (10-20 ml/30 min). Serum concentrations were not affected by the lavage.     

Impact of pharmacy outreach services on blood pressure management in the elderly community of Hong Kong

Aim: To investigate the impact of the Pharmacy Outreach Service (POS) on blood pressure (BP) and disease knowledge among community‐dwelling elderly patients with hypertension, and to evaluate the sustainability of such impact of POS. Methods: A prospective open‐labeled study of elderly adults (aged ≥65 years) with hypertension (BP ≥140/90 mmHg for non‐diabetics and ≥130/80 mmHg for diabetics) was carried out at seven elderly community centers from July 2008 to March 2010. Pharmacists provided BP monitoring, medication review and disease knowledge assessment. The target BP was <140/90 mmHg for non‐diabetics and <130/80 mmHg for diabetics. The primary outcome was BP change, whereas the secondary outcome was the change of disease knowledge of hypertension. All outcomes were compared between baseline and the last visit. For POS 2008/09 participants, BP was compared between values obtained during POS 2008/09 and 2009/10. Results: A total of 97 participants were recruited. Systolic BP reduced significantly from 152.38 ± 18.80 mmHg to 147.04 ± 20.72 mmHg (P = 0.021), and diastolic BP reduced from 73.84 ± 11.36 mmHg to 71.03 ± 10.97 mmHg (P = 0.010). Cumulative reductions in mean systolic BP and diastolic BP throughout the 2‐year study period were 21.39 ± 24.72 mmHg and 9.88 ± 13.48 mmHg, respectively (P < 0.001). A 12% increase in the at‐goal rate was observed in new participants recruited in 2009 (P = 0.039). Disease knowledge of hypertension improved significantly (P < 0.005), particularly in areas that included the definition of hypertension, diet and lifestyle modification. Conclusions: The POS might improve blood pressure control, hypertension and diabetes knowledge in elderly adults with hypertension in Hong Kong. The effect on blood pressure improvement was sustainable. Geriatr Gerontol Int 2013; 13: 175–181.     

T Cells Redirected to EphA2 for the Immunotherapy of Glioblastoma

Outcomes for patients with glioblastoma (GBM) remain poor despite aggressive multimodal therapy. Immunotherapy with genetically modified T cells expressing chimeric antigen receptors (CARs) targeting interleukin (IL)-13Rα2, epidermal growth factor receptor variant III (EGFRvIII), or human epidermal growth factor receptor 2 (HER2) has shown promise for the treatment of gliomas in preclinical models and in a clinical study (IL-13Rα2). However, targeting IL-13Rα2 and EGFRvIII is associated with the development of antigen loss variants, and there are safety concerns with targeting HER2. Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) has emerged as an attractive target for the immunotherapy of GBM as it is overexpressed in glioma and promotes its malignant phenotype. To generate EphA2-specific T cells, we constructed an EphA2-specific CAR with a CD28-ζ endodomain. EphA2-specific T cells recognized EphA2-positive glioma cells as judged by interferon-γ (IFN-γ) and IL-2 production and tumor cell killing. In addition, EphA2-specific T cells had potent activity against human glioma-initiating cells preventing neurosphere formation and destroying intact neurospheres in coculture assays. Adoptive transfer of EphA2-specific T cells resulted in the regression of glioma xenografts in severe combined immunodeficiency (SCID) mice and a significant survival advantage in comparison to untreated mice and mice treated with nontransduced T cells. Thus, EphA2-specific T-cell immunotherapy may be a promising approach for the treatment of EphA2-positive GBM.     

Polymyalgia rheumatica with drug eruption--an important differential diagnosis to dermatomyositis

With regard to certain clinical features, polymyalgia rheumatica (PR) may closely resemble dermatomyositis. In contrast to dermatomyositis, PR usually does not show any cutaneous manifestations, although there might be seen concomitant giant cell arteritis. Furthermore, we do not find muscle enzymes in the serum with PR, and there is no histologic evidence of myositis. In rare cases, however, PR may be associated with cutaneous drug eruption and/or non-specific increase of muscle enzymes, which might cause considerable difficulties regarding the diagnostic differentiation from dermatomyositis.     

Cytoskeleton and motility: an immunohistological and computer simulation analysis of melanocytic skin tumors

Tumor cell motility and tumor cell proliferation are supposed to be essential for tumor invasion. The cytoskeleton, which consists of different components, is considered to be important for maintaining cell shape and facilitating cell movement. Numerous data are available about tumor cell motility in vitro , but the behavior of tumor cells in vivo is as yet poorly understood. In the present study, estimates of tumor cell motility and proliferation were statistically derived from morphological tumor patterns in human melanocytic skin tumors, and their relationship to expression of certain cytoskeletal components was evaluated. Over-expression of vimentin within tumor cells correlated with low actual tumor cell motility and proliferation, indicating a structurally stabilizing function of these filaments. An overexpression of actin was found within tumor cells of high motility and proliferation, suggesting the contribution of cytocontractile elements to active tumor cell locomotion in situ. Concerning the cytoskeleton of the stromal cells, expression of actin, myosin and tubulin correlated with a high number of motile tumor cells and high mitotic counts. Thus increased tumor cell motility seems to be associated with cytoskeletal changes not only of the tumor cells themselves but also of the surrounding stromal cells.
Fink-Puches R, Smolle J. Cytoskeleton and motility: an immunohistological and computer simulation analysis of melanocytic skin tumors.     

6种液煤馏分的分离及其元素分析

采用柱层析法将６种不同地区的液煤馏分进行了分离并对其中两种液煤馏分的分离产物进行了元素分析。     

Inhibition of melanoma cell directional migration in vitro via different cellular targets

Abstract In malignant melanoma active movement of cancer cells is considered to be essential for tissue invasion. Various mechanisms, such as the Ca²⁺-calmodulin-proteinkinase C cascade or G-protein-dependent processes are considered to play a role in tumor cell functions. The assay of directional migration, combined with computer-assisted image analysis, was used to evaluate the antimigratory efficacy of drugs interfering with different steps of signal (ransduction pathways. Treatment with different compounds showed a more or less concentration-dependent reduction of migration rates: The Ca²⁺-channel blockers verapamil and devapamil showed a slight reduction of molility. The effect was more pronounced when the calmodulin antagonist flunarizine was used or the proteinkinase C inhibitors dequalinium, tamoxifen and H-7 were applied. A marked inhibition of molility was found with the G-protein antagonist L 651582. Thus, our results indicate that different signal transduclion pathways are involved in the regulation of directional migration of K1735-M2 melanoma cells.     

Prognostic evaluation of specific cutaneous infiltrates in B-chronic lymphocytic leukemia

The relationship between numerous histologic variables and survival was investigated in 54 consecutive lesions of specific skin infiltrates of B-cell chronic lymphocytic leukemia (B-CLL) from 27 patients (16 males and 11 females, mean age 65 years, range 42–83 years). All patients were followed for up to 204 months or until death. Histopathologically, the infiltrates showed a patchy perivascular (35%), diffuse (31.5%), nodular (31.5%) or band-like (1.9%) pattern. In 28% of the cases, an admixture of reactive cells within the infiltrate including eosinophils, histiocytes, neutrophils and plasma cells was observed. Cytomorphologically, small B-lymphocytes with condensed chromatin predominated in most infiltrates. However, some biopsies showed a small but significant number of medium- or large-sized neoplastic cells of the B-lymphocyte lineage with variable cytomorphological features. In a multivariate analysis, several histologic parameters within the infiltrates were found to show a significant association with long survival, namely, an infiltrate of moderate density, a nodular pattern, involvement of the lower dermis only, and presence of predominantly small B-lymphocytes (more than 95%) with condensed chromatin. Histologic variables that independently correlated with relatively short survival included an infiltrate of severe intensity, a diffuse pattern, epidermal changes (especially acanthosis and ulceration), medium-sized and large B-lymphocyte (more than 5%), and reactive cells within the infiltrate (neutrophils, eosinophils, and plasma cells). Overall analysis of our results showed two histologic patterns with a significant prognostic impact (p<0.01; z=5.4). Pattern I (33 biopsies) correlated with relatively long survival (2-year survival rate; 97%) and consisted of infiltrates showing predominantly small B-lymphocytes (more than 95%) without reactive cells or epidermal changes. Pattern II (21 biopsies) indicated short survival (2-year survival rate; 49%) and included all the rest of the biopsies i.e., infiltrates with medium- and large-sized B-lymphocytes (more than 5%), admixture of reactive cells, and epidermal changes. Results from our study suggest that histologic features in specific skin infiltrates of B-chronic lymphocytic leukemia may be helpful in identifying prognostically different subgroups of patients and planning therapeutic schedules.     

Interleukin-6 predicts hypoalbuminemia, hypocholesterolemia, and mortality in hemodialysis patients

Low serum albumin and low serum cholesterol levels are among the most consistent predictors of mortality in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Hypoalbuminemia is often interpreted as a marker of poor nutrition, but serum albumin and cholesterol levels can also be low as part of a cytokine-mediated acute-phase reaction to acute or chronic inflammation. Here we report the results from a 900-day prospective study designed to determine whether tumor necrosis factor-alfa (TNF-alpha) and interleukin-6 (IL-6) predict serum albumin and cholesterol levels and mortality in a group of 90 ambulatory, adult hemodialysis patients with no acute infection, hospitalization or surgery, and no known acquired immunodeficiency syndrome (AIDS), malignancy, or liver disease. Measurable levels of TNF-alpha and/or IL-6 were found in 89 of 90 patients. Significant relationships were found between TNF-alpha and IL-6 and the degree of hypoalbuminemia and dyslipoproteinemia. IL-6 was the strongest predictor of mortality in univariate and multivariate analysis, followed by age, albumin level, and body mass index (BMI). Although the cause of hypercytokinemia was not addressed in this study, the data support the view that hypoalbuminemia and hypocholesterolemia are negative acute-phase responses to inflammatory stimuli. These results suggest that efforts to identify the nature of the stimuli for cytokine production and to lower cytokine levels in hemodialysis patients might be effective in improving the survival of patients undergoing hemodialysis.