Cell lineage analysis of acute leukemia relapse uncovers the role of replication-rate heterogeneity and microsatellite instability

Human cancers display substantial intratumoral genetic heterogeneity, which facilitates tumor survival under changing microenvironmental conditions. Tumor substructure and its effect on disease progression and relapse are incompletely understood. In the present study, a high-throughput method that uses neutral somatic mutations accumulated in individual cells to reconstruct cell lineage trees was applied to hundreds of cells of human acute leukemia harvested from multiple patients at diagnosis and at relapse. The reconstructed cell lineage trees of patients with acute myeloid leukemia showed that leukemia cells at relapse were shallow (divide rarely) compared with cells at diagnosis and were closely related to their stem cell subpopulation, implying that in these instances relapse might have originated from rarely dividing stem cells. In contrast, among patients with acute lymphoid leukemia, no differences in cell depth were observed between diagnosis and relapse. In one case of chronic myeloid leukemia, at blast crisis, most of the cells at relapse were mismatch-repair deficient. In almost all leukemia cases, > 1 lineage was observed at relapse, indicating that diverse mechanisms can promote relapse in the same patient. In conclusion, diverse relapse mechanisms can be observed by systematic reconstruction of cell lineage trees of patients with leukemia.     

Actualización en la patología pulmonar relacionada con la infección VIH

The introduction of highly active antiretroviral therapy (HAART) has resulted in a reduction of opportunistic infections associated with cellular and humoral immunosuppression. However, what is still unclear is the impact of HAART on the development of other diseases not associated with AIDS, such as lung cancer and COPD. The aim of this paper is to review the most innovative and relevant aspects of lung pathology in patients infected with HIV.     

Visual lateralisation,form preferences,and secondary imprinting in the domestic chick

Newly hatched chicks (Exp. 1) were exposed to an imprinting object of a certain shape (sphere/cylinder) on Day 1 (primary imprinting) and then to a different-shaped object (cylinder/sphere) on Day 2 (secondary imprinting). They were tested on Day 3 for preferences between primary and secondary imprinting objects in binocular and monocular conditions. Right-eyed males, but not females, showed relatively stronger preferences for the primary imprinting object than left-eyed males; however, the asymmetry was modulated by a spontaneous preference for the sphere. In Experiment 2, a more traditional imprinting paradigm was used: chicks were exposed to the same object for the first 2 days, and on Day 3 underwent a free-choice test between the imprinting object (sphere/cylinder) and a novel one (cylinder/sphere). Results showed that no asymmetries in the use of eyes were apparent, only a general preference for the sphere. In Experiment 3 chicks were exposed, as in Experiment 1, to a primary (Day 1) and a secondary (Day 2) imprinting object; on Day 3 they were exposed to both objects simultaneously; they were also tested for preferences for the two stimuli on Day 4. Left- and right-eyed chicks showed different choice, with the latter preferring the cylinder, thus showing that the eye-asymmetry was in some way peculiar to the secondary imprinting procedure.     

Tratamiento quirúrgico de la mediastinitis necrosante descendente

Introduction

Descending necrotizing mediastinitis (DNM) is a serious infection which occurs as a complication of oropharyngeal infection. Its surgical management and the routine transthoracic approach remain controversial. In this article we report our experience in the management of this disease, and review the different surgical approaches that have been reported in the medical literature.

Material and methods

A retrospective review was made of the clinical records of 29 patients treated between 1988 and 2009. Several demographic variables were analyzed, origin of the initial infection, stage of the disease according to Endo's classification, surgical technique and outcome.

Results

Surgical treatment consisted of both cervical and mediastinal drainage and radical debridement. The mediastinal drainage was made through a transcervical approach in 10 cases and transthoracic in 19, depending on the extent of the mediastinitis. The outcome was satisfactory in 24 patients and 5 died (mortality 17.2%).

Conclusions

According to our results and the conclusions of the main authors, we recommend a prompt and aggressive surgery with a transthoracic approach in cases of widespread DNM.     

Wound healing potential of topical bacteriophage therapy on diabetic cutaneous wounds

Chronic wounds that fail to heal are a common complication of diabetes mellitus and the most common precipitating reason for nontraumatic lower limb amputation. Unfortunately, the bacterial species that cause these infections are becoming more resistant to antibiotics, making them increasingly difficult to treat. We assessed the feasibility of combating chronic bacterial infections with a topically delivered bacteriophage cocktail in two animal models of diabetes mellitus. Microbiological, planimetric, and histological parameters were compared in debrided infected wounds with or without topical bacteriophage treatment. We determined that bacteriophage treatment effectively decreased bacterial colony counts and improved wound healing, as indicated by smaller epithelial and dermal gaps, in Staphylococcus aureus and Pseudomonas aeruginosa infections but was not as effective against Acinetobacter baumannii. Although the improvements were more significant in the rodent model than in the porcine model, our results suggest that topically administered bacteriophage treatment may be effective in resolving chronic infections, especially when applied in conjunction with wound debridement. These findings have important implications for the feasibility of using topical antimicrobial therapies to safely treat chronic infections in diabetes mellitus patients.