Flow cytometry thresholds of myeloperoxidase detection to discriminate between acute lymphoblastic or myeloblastic leukaemia

The World Health Organization 2008 Classification emphasizes myeloperoxidase (MPO) detection as sufficient for assigning a blast population to the myeloid lineage. Published MPO positivity thresholds are 10% for flow cytometry (FCM) but 3% for cytochemistry. Here we re‐evaluated the FCM‐MPO threshold by comparing retrospectively 128 acute lymphoblastic leukaemias and 75 acute myeloid leukaemias without maturation, all assessed by benzidine‐based cytochemistry. A 13% threshold was found to be relevant using an isotype control as background‐reference (sensitivity 95·1%, specificity 91·7%). Residual normal lymphocytes proved to be an advantageous alternative reference, a threshold of 28% yielding improved 97·4% sensitivity and 96·1% specificity.     

Responses of mirror neurons in area F5 to hand and tool grasping observation

Mirror neurons are a distinct class of neurons that discharge both during the execution of a motor act and during observation of the same or similar motor act performed by another individual. However, the extent to which mirror neurons coding a motor act with a specific goal (e.g., grasping) might also respond to the observation of a motor act having the same goal, but achieved with artificial effectors, is not yet established. In the present study, we addressed this issue by recording mirror neurons from the ventral premotor cortex (area F5) of two monkeys trained to grasp objects with pliers. Neuron activity was recorded during the observation and execution of grasping performed with the hand, with pliers and during observation of an experimenter spearing food with a stick. The results showed that virtually all neurons responding to the observation of hand grasping also responded to the observation of grasping with pliers and, many of them to the observation of spearing with a stick. However, the intensity and pattern of the response differed among conditions. Hand grasping observation determined the earliest and the strongest discharge, while pliers grasping and spearing observation triggered weaker responses at longer latencies. We conclude that F5 grasping mirror neurons respond to the observation of a family of stimuli leading to the same goal. However, the response pattern depends upon the similarity between the observed motor act and the one executed by the hand, the natural motor template.     

An open-label, multicenter evaluation of the long-term safety and efficacy of risperidone in adolescents with schizophrenia

ABSTRACT: BACKGROUND: Data on the long-term efficacy, safety, and tolerability of risperidone in adolescents with schizophrenia are limited. The objective of this study was to evaluate the efficacy and safety of maintenance risperidone treatment in adolescents with schizophrenia. METHODS: This open-label study of adolescents aged 13 to 17 years with schizophrenia was a single extension study of two short-term double-blind risperidone studies and also enrolled subjects directly in open-label risperidone treatment. The risperidone dose was flexible and ranged from 2 to 6 mg/day. Most subjects enrolled for 6 months; a subset enrolled for 12 months. Assessment tools included the Positive and Negative Syndrome Scale total and factor scores, Clinical Global Impressions, Children's Global Assessment Scale, adverse event (AE) monitoring, vital signs, laboratory testing, and extrapyramidal symptom rating scales. RESULTS: A total of 390 subjects were enrolled; 48 subjects had received placebo in a previous double-blind study; 292 subjects had received risperidone as part of their participation in one of two previous controlled studies; and 50 subjects were enrolled directly for this study. A total of 279 subjects enrolled for 6 months of treatment, and 111 subjects enrolled for 12 months of treatment. Overall, 264 (67.7%) subjects completed this study: 209 of the 279 subjects (75%) in the 6-month group and 55 of the 111 subjects (50%) in the 12-month group. The median mode dose was 3.8 mg/day. At 6 months, all three groups experienced improvement from open-label baseline in symptoms of schizophrenia as well as general assessments of global functioning. Improvements were generally maintained for the duration of treatment. The most common AEs ([greater than or equal to]10% of subjects) were somnolence, headache, weight increase, hypertonia, insomnia, tremor, and psychosis. Potentially prolactin-related AEs (PPAEs) were reported by 36 (9%) subjects. The AE profile in this study was qualitatively similar to those of other studies in adult subjects with schizophrenia and in other psychiatric studies of risperidone in pediatric populations. CONCLUSIONS: Risperidone maintenance treatment in adolescents over 6 to 12 months was well tolerated, consistent with related studies in this clinical population, and associated with continued efficacy. Trial registration Clinical trials.gov registration number: NCT00246285 http://clinicaltrials.gov/ct2/show/NCT00246285?term=NCT00246285&rank=1.     

Comparative study of 23-gauge vitrectomy versus 20-gauge vitrectomy for the treatment of rhegmatogenous retinal detachment

Purpose  

To compare the safety and efficacy of 20- and 23-gauge pars plana vitrectomy (PPV) for the management of primary rhegmatogenous retinal detachment (RD) with proliferative vitreoretinopathy (PVR) grade B or less.     

RelB reduces thymocyte apoptosis and regulates terminal thymocyte maturation.

Thymocyte maturation is controlled by successive developmental checkpoints connected to the acquisition of a functional T cell receptor (TCR). During thymocyte selection, engagement of the TCR regulates the fine balance between death and survival signals. At the final stages of single-positive (SP) thymocyte maturation, the coupling of the TCR changes from death- to proliferation-inducing signals, a competence required for optimal effector functions in the periphery. We show here that in RelB mutant thymuses, thymocyte differentiation of CD24(-) SP cells is partially impaired. Competitive bone marrow reconstitution experiments show that this defect is constitutive to the lymphoid compartment. This is accompanied by an increased proportion of apoptotic thymocytes and a drastically reduced proliferation upon activation with anti-CD3 antibody/PMA stimulation. Thus, the RelB protein contributes to the quality of cell signaling in thymocytes by providing anti-apoptotic signals. These results suggest that in addition to its major role on the activation of antigen-presenting cell function, the RelB protein is intrinsically required for terminal thymocyte differentiation and activation.     

BAGE hypomethylation, a new epigenetic biomarker for colon cancer detection.

Early detection of colorectal cancer is a decisive step in the successful and complete cure of the disease. Epigenetic markers, in particular, those based on aberrant DNA methylation, can be used to diagnose cancer. B melanoma antigens (BAGE) are a family of genes and truncated genes located in the heterochromatic regions of several human chromosomes. Our previous work showed that BAGE loci (i.e., genes and truncated genes) were hypermethylated in normal tissues and hypomethylated in 98% of human cancers. In the present study, we analyzed DNA methylation of the BAGE loci in 54 colon cancers and in neighboring histopathologic normal tissue samples. Using a combined bisulfite restriction assay, we showed that BAGE loci were hypomethylated in 81% of carcinoma samples. Colon cancer could be diagnosed with 94% specificity, 83% sensitivity, and 89% accuracy. No correlation was found between DNA methylation of BAGE loci and age, gender of patients, nor with the tumor stage or site. Based on the hypothesis that during neoplastic transformation, hypomethylation occurs in juxtacentromeric CpG islands, we suggest that other genes located in the heterochromatic compartment should be tested. These new markers enrich the list of currently studied epigenetic alterations in colon cancer and could be associated with hypermethylation markers to develop reliable diagnostic tests.     

Intracrystalline proteins and urolithiasis: a synchrotron X-ray diffraction study of calcium oxalate monohydrate.

The existence of intracrystalline proteins and amino acids in calcium oxalate monohydrate was demonstrated by X-ray synchrotron diffraction studies. Their presence has implications for the destruction of calcium oxalate crystals formed in the urinary tract and the prevention of kidney stones. INTRODUCTION: Although proteins are present in human kidney stones, their role in stone pathogenesis remains unknown. This investigation aimed to characterize the nature of the relationship between the organic and mineral phases in calcium oxalate monohydrate (COM) crystals grown in human urine and in aqueous solutions of proteins and amino acids to clarify the function of proteins in urolithiasis. METHODS: COM crystals were grown in human urine and in aqueous solutions containing either human prothrombin (PT), Tamm-Horsfall glycoprotein (THG), aspartic acid (Asp), aspartic acid dimer (AspAsp), glutamic acid (Glu), glutamic acid dimer (GluGlu), or gamma-carboxyglutamic acid (Gla). Controls consisted of COM crystals precipitated from pure inorganic solutions or from human urine that had been ultrafiltered to remove macromolecules. Synchrotron X-ray diffraction with Rietveld whole-pattern peak fitting and profile analysis was used to determine nonuniform crystal strain and crystallite size in polycrystalline samples. RESULTS: Crystals precipitated from ultrafiltered urine had lower nonuniform strain than those grown in urine or in aqueous PT solution. Nonuniform strain was much lower in crystals grown in distilled water or in the presence of THG. For the amino acids, the highest nonuniform strain was exhibited by crystals grown in Gla solution, followed by Glu. Crystallite size was inversely related to nonuniform strain, with the effect being significantly less for amino acids than for macromolecules. CONCLUSIONS: Selected proteins and amino acids associated with COM crystals are intracrystalline. Although their incorporation into the mineral bulk would be expected to affect the rate of crystal growth, they also have the potential to influence the phagocytosis and intracellular destruction of any crystals nucleated and trapped within the renal collecting system. Crystals impregnated with protein would be more susceptible to digestion by cellular proteases, which would provide access to the crystal core, thereby facilitating further proteolytic degradation and mineral dissolution. We therefore propose that intracrystalline proteins may constitute a natural form of defense against renal stone formation.     

Trans-obturator surgery for stress urinary incontinence: 1-year follow-up of a cohort of 52 women

This study was a 1-year follow-up of a cohort of 52 women who underwent trans-obturator tape (TOT) procedures using Obtape. Follow-up information was available for 45/52 (87%) women. The rate of erosions was 8/52 (15%). Among 34 women examined, 26% experienced tenderness on palpation of operative site, and 72% were objectively cured on pad test. Forty women completed questionnaires (median Incontinence Impact Questionnaire-7, 0; median Urogenital Distress Inventory-6, 17) and of those, 93% would recommend TOT to a friend. We found a high rate of erosions among our cohort. Our high rate of erosions may be a result of our review of the majority of the cohort, and it is likely related to the specific device used (Obtape). The majority of women were satisfied with the outcome. Before introducing new procedures into widespread clinical practice, it is important to rigorously investigate their outcomes.