Characterization of primitive subpopulations of normal and leukemic cells present in the blood of patients with newly diagnosed as well as established chronic myeloid leukemia

Elevated numbers of primitive Philadelphia chromosome-positive (Ph+) progenitors, including long-term culture-initiating cells (LTC-IC) as well as colony-forming cells (CFC), have been previously described in the blood of patients with chronic myeloid leukemia (CML) in chronic phase with high white blood cell counts. In the present study, which focused primarily on an analysis of circulating progenitors present in such patients at diagnosis, we discovered the frequent and occasionally exclusive presence of circulating normal (Ph-) LTC-IC, often at levels above those seen for LTC-IC in the blood of normal individuals. The presence of detectable numbers of circulating Ph- LTC-IC was independent of the fact that the same peripheral blood samples also contained elevated numbers of predominantly or exclusively Ph+ CFC. Interestingly, both the Ph+ and Ph- LTC-IC in these samples were CD34+CD71- and variably CD38- and Thy-1+, as previously documented for LTC-IC in normal marrow. Thus, neither CD38 nor Thy-1 expression was useful for discriminating between Ph+ and Ph- LTC-IC in mixed populations. Nevertheless, an association of these phenotypes with LTC- IC function did allow highly enriched (> 5% pure) suspensions of either Ph+ or Ph- LTC-IC to be obtained from selected samples of CML blood in which the initial LTC-IC population was either predominantly Ph+ or Ph- , respectively. These findings suggest that the mechanisms causing mobilization of leukemic stem cells in untreated CML patients may affect their normal counterparts. They also indicate a possible new source of autologous cells for the support of intensive therapy of CML patients. Finally, they provide a method for obtaining the most highly purified populations of Ph+ LTC-IC described to date. This method should be useful for further analyses of the molecular activities of these very primitive neoplastic cells.     

Outcomes after liver transplantation for combined alcohol and hepatitis C virus infection

Alcohol abuse and chronic hepatitis C virus(HCV)infection are two major causes of chronic liver disease in the United States.About 10%-15%of liver transplants performed in the United States are for patients with cirrhosis due to combined alcohol and HCV infection.Data on outcomes on graft and patient survival,HCV recurrence,and relapse of alcohol use comparing transplants in hepatitis C positive drinkers compared to alcohol abuse or hepatitis C alone are conflicting in the literature.Some studies report a slightly better overall outcome in patients who were transplanted for alcoholic cirrhosis vs those transplanted for HCV alone or for combined HCV and alcohol related cirrhosis.However,some other studies do not support these observations.However,most studies are limited to a retrospective design or small sample size.Larger prospective multicenter studies are needed to better define the outcomes in hepatitis C drinkers.     

Mandibular advancement device and CPAP upon cardiovascular parameters in OSA

Purpose

This study aims to compare the effects of a mandibular advancement device (MAD) with continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea (OSA) on blood pressure (BP), oxidative stress, and heart rate variability (HRV) in a randomized, crossed-over, single-blind, and controlled trial.

Methods

Twenty-nine moderate-to-severe adult OSA patients underwent MAD, CPAP, and placebo oral appliance treatment. Polysomnography, Epworth sleepiness scale, 24-h ambulatory BP monitoring, oxidative stress parameters (malondialdehyde, catalase, superoxide dismutase, vitamins C, E, B₆, B₁₂, folate, homocysteine, uric acid), and HRV were assessed at baseline and after 1 month of each treatment. Diaries were used to evaluate compliance for devices and a pressure–time meter for CPAP.

Results

Both active treatments resulted in decreases in apnea and hypopnea index and Epworth sleepiness scale; CPAP showed a greater effect. Frequency of diastolic BP dipping was higher in the MAD group compared with the CPAP group. A significant drop from baseline levels for catalase activity was observed after MAD. For HRV, there was a significant decrease in total power at night with CPAP and MAD compared with POA, and a decrease in index of sleep autonomic variation with MAD compared with baseline levels. Compliance rates were higher with MAD rather than CPAP.

Conclusions

Even though CPAP proved to be more effective at attenuating OSA, better compliance with MAD favored the reduction of one of the enzymes which participates in oxidative stress and better autonomic modulation during sleep.     

Copy number variants in patients with short stature

Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals can lead to the discovery of novel rare gene defects with a large effect on growth. In an effort to identify novel genes associated with short stature, genome-wide analysis for copy number variants (CNVs), using single-nucleotide polymorphism arrays, in 162 patients (149 families) with short stature was performed. Segregation analysis was performed if possible, and genes in CNVs were compared with information from GWAS, gene expression in rodents'' growth plates and published information. CNVs were detected in 40 families. In six families, a known cause of short stature was found (SHOX deletion or duplication, IGF1R deletion), in two combined with a de novo potentially pathogenic CNV. Thirty-three families had one or more potentially pathogenic CNVs (n=40). In 24 of these families, segregation analysis could be performed, identifying three de novo CNVs and nine CNVs segregating with short stature. Four were located near loci associated with height in GWAS (ADAMTS17, TULP4, PRKG2/BMP3 and PAPPA). Besides six CNVs known to be causative for short stature, 40 CNVs with possible pathogenicity were identified. Segregation studies and bioinformatics analysis suggested various potential candidate genes.     

Sleep Apnea and Nocturnal Cardiac Arrhythmia: A Populational Study

Background

The mechanisms associated with the cardiovascular consequences of obstructive sleep apnea include abrupt changes in autonomic tone, which can trigger cardiac arrhythmias. The authors hypothesized that nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea.

Objective

To analyze the relationship between obstructive sleep apnea and abnormal heart rhythm during sleep in a population sample.

Methods

Cross-sectional study with 1,101 volunteers, who form a representative sample of the city of São Paulo. The overnight polysomnography was performed using an EMBLA® S7000 digital system during the regular sleep schedule of the individual. The electrocardiogram channel was extracted, duplicated, and then analyzed using a Holter (Cardio Smart®) system.

Results

A total of 767 participants (461 men) with a mean age of 42.00 ± 0.53 years, were included in the analysis. At least one type of nocturnal cardiac rhythm disturbance (atrial/ventricular arrhythmia or beat) was observed in 62.7% of the sample. The occurrence of nocturnal cardiac arrhythmias was more frequent with increased disease severity. Rhythm disturbance was observed in 53.3% of the sample without breathing sleep disorders, whereas 92.3% of patients with severe obstructive sleep apnea showed cardiac arrhythmia. Isolated atrial and ventricular ectopy was more frequent in patients with moderate/severe obstructive sleep apnea when compared to controls (p < 0.001). After controlling for potential confounding factors, age, sex and apnea-hypopnea index were associated with nocturnal cardiac arrhythmia.

Conclusion

Nocturnal cardiac arrhythmia occurs more frequently in patients with obstructive sleep apnea and the prevalence increases with disease severity. Age, sex, and the Apnea-hypopnea index were predictors of arrhythmia in this sample.     

Swallowing in Patients with Parkinson’s Disease: A Surface Electromyography Study

Our goal was to study deglutition of Parkinson??s disease (PD) patients and normal controls (NC) using surface electromyography (sEMG). The study included 15 patients with idiopathic PD and 15 age-matched normal controls. Surface electromyography was collected over the suprahyoid muscle group. Conditions were the following: swallow at once 10 and 20?ml of water and 5 and 10?ml of yogurt of firm consistency, and freely drink 100?ml of water. During swallowing, durations of sEMG were significantly longer in PD patients than in normal controls but no significant differences of amplitudes were found. Eighty percent of the PD patients and 20?% of the NC needed more than one swallow to consume 20?ml of water, while 70?% of the PD patients and none of the NC needed more than one swallow to consume 5?ml of yogurt. PD patients took significantly more time and needed significantly more swallows to drink 100?ml of water than normal controls. We conclude that sEMG might be a simple and useful tool to study and monitor deglutition in PD patients.     

Comparison of the effects of continuous positive airway pressure,oral appliance and exercise training in obstructive sleep apnea syndrome

OBJECTIVE:

There are several treatments for obstructive sleep apnea syndrome, such as weight loss, use of an oral appliance and continuous positive airway pressure, that can be used to reduce the signs and symptoms of obstructive sleep apnea syndrome. Few studies have evaluated the effectiveness of a physical training program compared with other treatments. The aim of this study was to assess the effects of physical exercise on subjective and objective sleep parameters, quality of life and mood in obstructive sleep apnea patients and to compare these effects with the effects of continuous positive airway pressure and oral appliance treatments.

METHODS:

Male patients with moderate to severe obstructive sleep apnea and body mass indices less than 30 kg/m2 were randomly assigned to three groups: continuous positive airway pressure (n = 9), oral appliance (n = 9) and physical exercise (n = 7). Polysomnographic recordings, blood samples and daytime sleepiness measurements were obtained prior to and after two months of physical exercise or treatment with continuous positive airway pressure or an oral appliance. Clinicaltrials.gov: NCT01289392

RESULTS:

After treatment with continuous positive airway pressure or an oral appliance, the patients presented with a significant reduction in the apnea-hypopnea index. We did not observe changes in the sleep parameters studied in the physical exercise group. However, this group presented reductions in the following parameters: T leukocytes, very-low-density lipoprotein and triglycerides. Two months of exercise training also had a positive impact on subjective daytime sleepiness.

CONCLUSIONS:

Our results suggest that isolated physical exercise training was able to modify only subjective daytime sleepiness and some blood measures. Continuous positive airway pressure and oral appliances modified the apnea-hypopnea index.     

Laser Doppler anemometry measurements of steady flow through two bi-leaflet prosthetic heart valves

Introduction

In vitro hydrodynamic characterization of prosthetic heart valves provides important information regarding their operation, especially if performed by noninvasive techniques of anemometry. Once velocity profiles for each valve are provided, it is possible to compare them in terms of hydrodynamic performance. In this first experimental study using laser doppler anemometry with mechanical valves, the simulations were performed at a steady flow workbench.

Objective

To compare unidimensional velocity profiles at the central plane of two bi-leaflet aortic prosthesis from St. Jude (AGN 21 - 751 and 21 AJ - 501 models) exposed to a steady flow regime, on four distinct sections, three downstream and one upstream.

Methods

To provide similar conditions for the flow through each prosthesis by a steady flow workbench (water, flow rate of 17L/min. ) and, for the same sections and sweeps, to obtain the velocity profiles of each heart valve by unidimensional measurements.

Results

It was found that higher velocities correspond to the prosthesis with smaller inner diameter and instabilities of flow are larger as the section of interest is closer to the valve. Regions of recirculation, stagnation of flow, low pressure, and flow peak velocities were also found.

Conclusions

Considering the hydrodynamic aspect and for every section measured, it could be concluded that the prosthesis model AGN 21 - 751 (RegentTM) is superior to the 21 AJ - 501 model (Master Series). Based on the results, future studies can choose to focus on specific regions of the these valves.