Long-term outcome of autologous transplantation of peripheral blood progenitor cells as postremission management of patients > or =60 years with acute myelogenous leukemia.

The optimal postremission treatment for elderly patients with acute myelogenous leukemia (AML) is presently unknown, but recent studies report the feasibility of autologous stem cell transplantation in this population. To better understand the long-term outcome of autologous transplantation in AML patients > or =60 years of age, we evaluated high-dose chemoradiotherapy preparative conditioning followed by transplantation of peripheral blood progenitor cells procured after a single cycle of cytarabine-based consolidation chemotherapy as postremission therapy in 27 patients aged 60 to 71 years (median age, 65 years) with newly diagnosed AML in first complete remission (CR). The median follow-up from CR for all patients was 13.6 months (range, 6.0-123.1 months). The median follow-up from remission for surviving patients was 81 months (range, 41.4-123.1 months). Seven patients are alive in continuous CR, 19 died from relapse, and 1 died as a result of treatment-related infection. Leukemia-free survival and overall survival are 10.3 and 13.4 months, respectively. Actuarial leukemia-free and overall survival at 3 years are 25% +/- 9% and 28% +/- 9%, respectively. Our results demonstrate that autologous transplantation of peripheral blood progenitor cells is well tolerated and feasible for patients > or =60 years of age with AML in first CR. Future investigation should focus on a randomized study evaluating a larger group of elderly patients in first CR comparing autologous stem cell transplantation with conventional cytarabine-based consolidation chemotherapy to identify the optimal postremission therapy.     

Visceral leishmanisis in paediatrics: a study of 367 cases in southwest Iran

Kala-azar (visceral leishmaniasis [VL]) is endemic in southern Iran. We retrospectively evaluated 367 infants and children suffering from VL at hospitals affiliated to the Shiraz University of Medical Sciences in Fars Province, southwest Iran). Seasonal variations were observed with more cases presenting in late winter, spring and fewer in summer. The predominant clinical features in these patients were chronic fever, pallor, weight loss, abdominal distention and hepatosplenomegaly. Lymphadenopathy was less common. Common laboratory abnormalities included anaemia, leukopenia, thrombocytopenia, hypoalbuminaemia and hypergammaglobulinaemia. Liver function tests were deranged in two-thirds of the patients. The immunofluorescence antibody test was positive in all patients and all of them had a positive bone marrow smear or a culture for Leishmania donovani. Patients responded well to glucantim therapy with a cure rate of 96.7%. Relapse was observed in 8.2% (30). Mortality in this series was 7.3%. Twenty patients died during their therapy period. Jaundice and grossly deranged liver function tests were found to be bad prognostic signs.     

Fucosyltransferase 4 and 7 mediates adhesion of non-small cell lung cancer cells to brain-derived endothelial cells and results in modification of the blood–brain-barrier: in vitro investigation of CD15 and CD15s in lung-to-brain metastasis

Purpose

Metastatic non-small cell lung (NSCLC) cancer represents one of the most common types of brain metastasis. The mechanisms involved in how circulating cancer cells transmigrate into brain parenchyma are not fully understood. The aim of this work was to investigate the role of fucosylated carbohydrate epitopes CD15 and sialyated CD15s in cancer adhesion to brain-derived endothelial cells and determine their influence in blood–brain barrier (BBB) disruption

Methods

Three distinct, independent methods were used to measure brain endothelial integrity and include voltohmmeter (EVOM?), impedance spectroscopy (CellZscope®) and electric cell-substrate impedance sensing system (ECIS?). Two fucosyltransferases (FUT4 and 7) responsible for CD15 and CD15s synthesis were modulated in four human cancer cell lines (three lung cancer and one glioma).

Results

Overexpression of CD15 or CD15s epitopes led to increase in adhesion of cancer cells to cerebral endothelial cells compared with wild-type and cells with silenced CD15 or CD15s (p?<?0.01). This overexpression led to the disruption of cerebral endothelial cell monolayers (p?<?0.01). Knockdown of FUT4 and FUT7 in metastatic cancer cells prevented disruption of an in vitro BBB model. Surprisingly, although the cells characterised as ‘non-metastatic’, they became ‘metastatic’ -like when cells were forced to over-express either FUT4 or FUT7.

Conclusions

Results from these studies suggest that overexpression of CD15 and CD15s could potentiate the transmigration of circulating NSCLC cells into the brain. The clinical significance of these studies includes the possible use of these epitopes as biomarkers for metastasis.

     

Non-motor outcomes of subthalamic stimulation in Parkinson's disease depend on location of active contacts

Background

Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in Parkinson's disease (PD). Few studies have investigated the influence of the location of neurostimulation on NMS.

Standards for Detecting,Interpreting, and Reporting Noncontrast Computed Tomographic Markers of Intracerebral Hemorrhage Expansion

Significant hematoma expansion (HE) affects one‐fifth of people within 24 hours after acute intracerebral hemorrhage (ICH), and its prevention is an appealing treatment target. Although the computed tomography (CT)‐angiography spot sign predicts HE, only a minority of ICH patients receive contrast injection. Conversely, noncontrast CT (NCCT) is used to diagnose nearly all ICH, so NCCT markers represent a widely available alternative for prediction of HE. However, different NCCT signs describe similar features, with lack of consensus on the optimal image acquisition protocol, assessment, terminology, and diagnostic criteria. In this review, we propose practical guidelines for detecting, interpreting, and reporting NCCT predictors of HE. ANN NEUROL 2019;86:480–492     

Induced pluripotent stem cells--opportunities for disease modelling and drug discovery

The ability to generate induced pluripotent stem cells (iPSCs) from patients, and an increasingly refined capacity to differentiate these iPSCs into disease-relevant cell types, promises a new paradigm in drug development - one that positions human disease pathophysiology at the core of preclinical drug discovery. Disease models derived from iPSCs that manifest cellular disease phenotypes have been established for several monogenic diseases, but iPSCs can likewise be used for phenotype-based drug screens in complex diseases for which the underlying genetic mechanism is unknown. Here, we highlight recent advances as well as limitations in the use of iPSC technology for modelling a 'disease in a dish' and for testing compounds against human disease phenotypes in vitro. We discuss how iPSCs are being exploited to illuminate disease pathophysiology, identify novel drug targets and enhance the probability of clinical success of new drugs.     

Study on cryptosporidiosis incidence in broilers in Garmsar region, Iran

This study was carried out to determine the incidence rate of cryptosporidiosis in Garmsar broilers and the factors associated with this infection. Two hundred forty histopathology samples were randomly collected from the intestine and trachea of broilers in six different age groups. After sample preparation and staining with H&E, sections were studied by light microscopy for the presence of Cryptosporidium species. The results demonstrated that 23.75% of broilers were totally infected. There were 10.83% of samples that had an infection only in the intestine and 4.58% had an infection only in the trachea. The infection rate for both the trachea and intestine was 8.33%. Statistical analysis revealed that the age of the broiler was significantly associated with an increase risk of infection, the highest incidence rate of infection was in the 21–25-day-old group and the minimum infection rate was in the 10–15-day-old group. Incidence rate of infection was significant with respect to different age groups, hygiene condition, and nutritional status, but the incidence rate of infection was not significant in different geographical parts of Garmsar region.