Use of pentoxifylline as an inhibitor of free radical generation in peripheral vascular disease

Summary The effects of an infusion of pentoxifylline 1 g as an inhibitor of free radical generation have been determined in a double-blind placebo-controlled study. Leucocyte-derived free radical generation (by the superoxide dismutase-inhibitable reduction of ferricytochrome), the release of reactive oxygen metabolites (as plasma oxidant activity), unfractionated leucocyte and erythrocyte filterability rates (using a constant-flow positive-pressure system), plasma viscosity, and plasma fibrinogen concentration have been measured in two matched groups of 10 patients with Stage II peripheral vascular disease, before and after treatment. Transcutaneous oxygen pressure (P_tcO₂) during treadmill exercise to stress leg circulation was also measured.Leucocyte-derived free radicals were generated during peripheral ischaemia. Pentoxifylline inhibited their generation, blocked the release of reactive oxygen metabolites, and reduced impairment of the filterability rate of unfractionated leucocytes.The improvements were accompanied by significant shortening of the half-time of recovery of transcutaneous oxygen pressure, indicating that ischaemic damage had been contained.     

Evaluation of the soluble fragments of cytokeratin 19 (CK19) in non-small cell lung cancer (NSCLC)

This study compared the diagnostic efficacy of serum CK19 determination (Cyfra 21-1) with other tumour markers, such as CEA, SCC, NSE, TPA, in patients with resected non-small lung cancer. Tumour marker levels were tested in 90 patients with benign lung disease and at diagnosis in 72 patients with proven NSCLC, 39 squamous cell carcinoma and 33 adenocarcinoma. At presentation baseline levels of all tumor markers were significantly higher (p<0.05) in lung cancer patients than in control subjects, except for NSE. A significant increase (p<0.05) in serum concentrations was observed from stage I to stage IIIb only for Cyfra 21-1 (stage I/II, median=2.7 ng/ml; stage IIIb, median=6.3 ng/ml) and TPA (stage I/II, median=89.8 IU/ml; stage IIIb, median=170.7 IU/ml). Receiver operating characteristic (ROC) analysis was performed to evaluate the best threshold values and the global accuracy of each marker. The highest global sensitivity for NSCLC was reached by TPA (70.8%), whereas that of Cyfra 21-1 was 50%. According to tumour histology, significant difference (p<0.05) in serum levels were found only for CEA (adenocarcinomas, median=5.6 ng/ml; squamous cell carcinoma, median=3.2 ng/ml) and SCC (adenocarcinomas, median=1.0 ng/ml; squamous cell carcinoma, median=1.5 ng/ml). As regards squamous cell carcinoma histotype, the highest sensitivity was obtained by TPA (74.4% at a specificity of 62.2%) and for adenocarcinomas by CEA (78.8% at a specificity of 85.6%). Tumour marker levels were also determined during the follow-up of 10 patients. The best sensitivity in detecting relapses was shown by CEA (90%), followed by TPA (70%), SCC (50%), Cyfra 21-1 (40%) and NSE (10%), even though the CEA test displayed a high percentage of false positive results (98.1%) in patients with no evidence of disease (NED).     

Long-Acting Injectable Antipsychotics in Schizophrenia: Literature Review and Practical Perspective,with a Focus on Aripiprazole Once-Monthly

Introduction

Prevention of relapse is a major challenge in schizophrenia, a disease characterized by poor adherence to antipsychotic medication leading to multiple rehospitalizations and a substantial burden-of-care.

Methods

We narratively review published clinical data from the development of long-acting injectable (LAI) formulations of antipsychotic drugs and examine the comparative effectiveness of oral versus LAIs in schizophrenia, with a focus on the second-generation LAI antipsychotic aripiprazole. Evidence is presented from studies with naturalistic/pragmatic as well as explanatory trial designs, supported by the clinical experience of the authors.

Results

LAI formulations of antipsychotic drugs offer advantages over oral medications and there is good evidence for their use as a first-choice treatment and in younger patients. Key phase III studies have shown aripiprazole once-monthly 400 mg (AOM 400) to be effective and well tolerated, with high rates of adherence and low rates of impending relapse. In a recent randomized trial with a “naturalistic” study design more representative of routine clinical practice, AOM 400 was well tolerated and had significantly greater effectiveness than paliperidone LAI overall and in younger patients aged ≤35 years.

Conclusion

Results across the “full spectrum” of efficacy in traditional clinical trials as well as those encompassing the concept of effectiveness in a more naturalistic setting of real-life clinical practice support the use of AOM 400 as a valid long-term treatment option in schizophrenia overall, as well as earlier in the treatment course, and not solely in situations of poor adherence or when oral antipsychotics have failed.

     

Generation of renal Epo-producing cell lines by conditional gene tagging reveals rapid HIF-2 driven Epo kinetics,cell autonomous feedback regulation,and a telocyte phenotype

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Inferior vena cava thrombosis: an unusual complication of a large simple non-parasitic liver cyst requiring an integrated approach

Most of the simple hepatic cysts are asymptomatic and have a benign course. However, some exceptional life-threatening complications may occur. We herein report the successful management of a case who suffered from a cystic compression of the inferior vena cava complicated by thrombosis of the inferior vena cava itself. To our knowledge this is the first report of such a complication and diagnostic and therapeutic aspects are discussed. This case is paradigmatic of the possible complexity of the diagnosis and treatment of cystic lesions of the liver and should induce physicians to consider a therapeutic approach if a clear tendency to enlarge can be recognized.     

Developmental plasticity of CNS microglia

Microglia arise from CD45(+) bone marrow precursors that colonize the fetal brain and play a key role in central nervous system inflammatory conditions. We report that parenchymal microglia are uncommitted myeloid progenitors of immature dendritic cells and macrophages by several criteria, including surface expression of "empty" class II MHC protein and their cysteine protease (cathepsin) profile. Microglia express receptors for stem cell factor and can be skewed toward more dendritic cell or macrophage-like profiles in response to the lineage growth factors granulocyte/macrophage colony-stimulating factor or macrophage colony-stimulating factor. Thus, in contrast to other organs, where terminally differentiated populations of resident dendritic cells and/or macrophages outnumber colonizing precursors, the majority of microglia within the brain remain in an undifferentiated state.     

Video-assisted sleeve lobectomy for mucoepidermoid carcinoma of the left lower lobar bronchus: a case report

We report what we believe to be the first case of video-assisted sleeve lobectomy in an adolescent girl who had experienced recurrent episodes of lobar pneumonia and received a diagnosis of low-grade mucoepidermoid carcinoma of the left lower lobar bronchus.     

Strong iron demand during hypoxia-induced erythropoiesis is associated with down-regulation of iron-related proteins and myoglobin in human skeletal muscle

Iron is essential for oxygen transport because it is incorporated in the heme of the oxygen-binding proteins hemoglobin and myoglobin. An interaction between iron homeostasis and oxygen regulation is further suggested during hypoxia, in which hemoglobin and myoglobin syntheses have been reported to increase. This study gives new insights into the changes in iron content and iron-oxygen interactions during enhanced erythropoiesis by simultaneously analyzing blood and muscle samples in humans exposed to 7 to 9 days of high altitude hypoxia (HA). HA up-regulates iron acquisition by erythroid cells, mobilizes body iron, and increases hemoglobin concentration. However, contrary to our hypothesis that muscle iron proteins and myoglobin would also be up-regulated during HA, this study shows that HA lowers myoglobin expression by 35% and down-regulates iron-related proteins in skeletal muscle, as evidenced by decreases in L-ferritin (43%), transferrin receptor (TfR; 50%), and total iron content (37%). This parallel decrease in L-ferritin and TfR in HA occurs independently of increased hypoxia-inducible factor 1 (HIF-1) mRNA levels and unchanged binding activity of iron regulatory proteins, but concurrently with increased ferroportin mRNA levels, suggesting enhanced iron export. Thus, in HA, the elevated iron requirement associated with enhanced erythropoiesis presumably elicits iron mobilization and myoglobin down-modulation, suggesting an altered muscle oxygen homeostasis.